EMERALD trial analysis of patient-reported outcomes (PROs) in patients with ER+/HER2- advanced or metastatic breast cancer (mBC) comparing oral elacestrant vs standard of care (SoC) endocrine therapy

Background: The phase III EMERALD trial (NCT03778931) reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with elacestrant vs SoC endocrine therapy (ET) in patients (N=478) with ER+/HER2- advanced or mBC following progression on prior CDK4/6i plus ET. PROs measuring quality of life (QoL) are reported here. Method(s): EMERALD patients (pts) completed 3 PRO tools at prespecified time points: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the EuroQoL 5 Dimension 5 Level (EQ-5D-5L). Result(s): The ratio of PROs tools completed vs. PROs tools expected was 80-90% through cycle 4 and approximately 70% at cycle 6;likely due to clinical study period overlapping with COVID-19 period. Overall, the EORTC QLQ-C30 scores were similar for elacestrant and SoC, with no differences across all time points for both functional and symptom scales. However, PRO-CTCAE results showed that fewer pts who received elacestrant reported very severe nausea (4.0% vs 14.3% by cycle 6) or very severe vomiting (9.1% vs 50% by cycle 6) compared with SoC. There were no clinically meaningful differences across all time points in adverse events typically observed with pts with cancer on ET, such as fatigue, nausea, vomiting, joint and muscle pain and hot flashes. EQ-5D-5L scores were generally comparable throughout treatment for both study arms, with elacestrant showing numerically better outcomes vs SoC for mobility, self-care and usual activities. Similar trends were observed for the full intent-to-treat population and in pts with detectable estrogen receptor 1 mutations (ESR1m). Conclusion(s): This analysis confirmed that QoL was maintained between treatment groups in the EMERALD trial. Together with the previously described statistically significant prolonged PFS and manageable safety profile, these PRO results provide additional evidence that oral elacestrant is clinically meaningful in this patient population with limited therapeutic options. Clinical trial identification: NCT03778931. Editorial acknowledgement: Jeffrey Walter, IQVIA. Legal entity responsible for the study: Stemline Therapeutics/Menarini Group. Funding(s): Stemline Therapeutics/Menarini Group. Disclosure: J. Cortes: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics;Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo;Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies;Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics;Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London;Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. F.C. Bidard: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Radius Health, Menarini;Financial Interests, Institutional, Advisory Role: Menarini;Financial Interests, Personal, Speaker's Bureau: Pfizer, Novartis, AstraZeneca, Roche, Lilly, Rain Therapeutics;Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Menarini Silicon Biosystems, Prolynx;Financial Interests, Institutional, Other, patents: ESR1 & MSI detection techniques;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca, Novartis. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisa , Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead;Financial Interests, Personal, Royalties: UpToDate;Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.;Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. V.G. Kaklamani: Financial Interests, Personal, Other, Honoraria: Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, Daichi, Gilead Sciences;Financial Interests, Personal, Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, Athenex, bioTheranostics;Financial Interests, Personal, Speaker's Bureau: Genentech, Novartis, Genomic Health, Puma Biotechnology, Pfizer, AstraZeneca/Daiichi Sankyo;Financial Interests, Personal, Research Grant: Eisai. I. Vlachaki: Financial Interests, Personal, Full or part-time Employment: Menarini Hellas A.E. G. Tonini: Financial Interests, Personal, Full or part-time Employment: Menarini Ricerche S.p.A. N. Habboubi: Financial Interests, Personal, Full or part-time Employment: Stemline Therapeutics;Financial Interests, Personal, Leadership Role: Stemline Therapeutics. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly;Financial Interests, Personal, Invited Speaker: Synthon, Amgen;Financial Interests, Institutional, Research Grant: Roche.Copyright © 2023

Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816

Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.

Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

Cancer survivors' perceptions of priorities for geriatric oncology research: A qualitative study

Background: People living with and after cancer may experience complex physical and psychosocial issues requiring multidisciplinary support. While adults over the age of 65 are the group most commonly diagnosed with cancer, they also represent the group most under-represented in research. Therefore, this study aims to explore older adults' perceptions of priorities for research in cancer and haematological malignancies. Methods: A descriptive qualitative study was undertaken with sixteen older adults over the age of 65 who were living with or after a diagnosis of cancer. Participants were purposively recruited via a regional cancer centre and cancer advocacy organisations. Participants engaged in a one-to-one semi-structured telephone interview, which discussed their experiences of cancer, and their perceptions of cancer-related issues which they believed were priorities for research in the future. Qualitative data were thematically analysed. Results: Participants were overwhelmingly satisfied with the cancer-related care they received, but discussed a variety of issues related to their experiences of information, symptoms, and support beyond the hospital setting which warranted further research. Forty-two priorities for future research were categorised within six themes, containing a total of eleven sub-themes. Priorities for future research included the recognition of the signs and symptoms of cancer in older adulthood;research about cancer treatments for older adults;supporting the assessment and management of co-morbidities;the unmet needs of older adults living with and after cancer;the impact of COVID-19 on people living with or after cancer and on cancer services;and the impact of cancer on caregivers and family members. Conclusions: The results of this study represent a basis for future priority setting for research in the field of geriatric oncology. The results of this study have the potential to underpin priorities for research which are driven by the population who are most affected by, and most in need of research to address the complex issues associated with diagnosis, treatment, survivorship, and end of life care for people living with or after cancer in older adulthood. Legal entity responsible for the study: University College Dublin. Funding: Irish Research Council. Disclosure: A. Drury: Financial Interests, Personal, Full or part-time Employment: University College Dublin;Financial Interests, Institutional, Research Grant, I am a collaborator on the Pfizer-funded project ABC4Nurses, which is coordinated and managed by EONS: Pfizer;Non-Financial Interests, Invited Speaker: European Oncology Nursing Society;Non-Financial Interests, Advisory Role, I am an advisor on several EONS projects, including ABC4Nurses and RCC & HCC PROMS: European Oncology Nursing Society. All other authors have declared no conflicts of interest.

Net treatment benefit of OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in phase III Atalante-1 randomized trial

Background: OSE2101 (Tedopi) is an anticancer vaccine that increased overall survival (OS) (HR 0.59, p=0.017) versus Standard of Care Chemotherapy in the population of interest (PoI N=118) of patients with IO secondary resistance after sequential CT-IO (ESMO 2021 #47LBA). The Net Treatment Benefit (NTB) is an original method combining efficacy and safety endpoints to test the overall improvement in health outcome between 2 treatments (Buyse M. Stat Med 2010). NTB was assessed in the overall population (N=219) from whom OS improvement of OSE2101 (HR 0.86, p=0.35) was lower than in PoI. Methods: NTB was tested by comparing prioritized outcomes using Generalized Paired Wise Comparisons (GPC). The prioritized outcomes were OS, then time to worsening ECOG (threshold=2 months) followed by severe adverse events, progression free survival (shorter vs. longer than 2 months) and Quality of Life (threshold=5 points on Global Health Status of EORTC-QLQC30). Analysis was stratified using the 3 strata of the study (histology, best response to 1rst line, line of prior IO) and enrollment time (before vs during COVID-19). Sensitivity analyses used no stratification, different thresholds of clinical relevance and PoI. Results: In the primary analysis (1088 pairs), NTB was 19% and reached statistical significance in favor of OSE2101 (p=0.035). In unstratified analysis (11120 pairs), NTB was 11% (p=0.188). In the PoI (388 pairs), NTB was 22% (p stratified=0.074) and 28% (p=0.014) in unstratified analysis (3040 pairs). Although the primary analysis was statistically positive, results were not consistent in some sensitivity analyses due to the limited sample size and the impact of stratification factors. Conclusions: An overall improvement in health outcome was observed with OSE2101 in the overall population of advanced NSCLC after IO failure with a NTB of 19% over SoC. In PoI with IO secondary resistance after CT-IO, the NTB was 22%. Post-hoc analyses are ongoing intended to explain the variability of NTB and will be detailed. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD) for his support in the writing of the . Legal entity responsible for the study: Ose Immunotherapeutics. Funding: Ose Immunotherapeutics. Disclosure: M.E. Buyse: Financial Interests, Personal, Officer, Chief Scientific Officer: IDDI;Financial Interests, Personal, Invited Speaker, Board Member: CluePoints;Financial Interests, Personal, Stocks/Shares: IDDI, CluePoints. F. Montestruc: Financial Interests, Personal, Member of the Board of Directors, CEO of the Company: eXYSTAT SAS;Financial Interests, Institutional, Other, Statistician Consultant: AbbVie, Biocodex, Geneuro, Gensight, Guerbet, Imcheck, Ose Immunotherapeutics, Pfizer, Takeda;Non-Financial Interests, Personal, Other, Statistician Consultant and Training: Institut Pasteur. J. Chiem: Financial Interests, Personal, Full or part-time Employment: IDDI. V. Deltuvaite-Thomas: Financial Interests, Personal, Full or part-time Employment: IDDI. S. Salvaggio: Financial Interests, Personal, Full or part-time Employment, Working as a statistician: International Drug Development Institute. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Role: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology;Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech, MSD Oncology, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD;Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MS . S. Viteri Ramirez: Financial Interests, Personal, Advisory Board: Merck Healthcare KGAA Germany, Bristol Myers Squibb S.A. U, Puma Biotechnology;Financial Interests, Personal, Invited Speaker: Takeda Farmaceutica España SA, MSD de España SA, AstraZeneca Farmaceutica Spain, Roche Farma SA;Financial Interests, Personal, Expert Testimony: Reddy Pharma Iberia SAU. W. Schuette: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Novartis;Financial Interests, Personal, Advisory Role: Roche, MSD, Novartis. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost;Financial Interests, Personal, Stocks/Shares: Nixio;Financial Interests, Institutional, Research Grant: BMS. S. Comis: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics;Financial Interests, Personal, Other, Actions: Ose Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Pfizer, Takeda, Regeneron, MSD, Bristol Myers-Squibb, PharmaMar, Bayer;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Foundation Medicine;Financial Interests, Personal, Expert Testimony: Novartis;Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo;Financial Interests, Invited Speaker: BeiGene, Ardigen, Ose Immunotherapeutics;Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma;Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche;Other, Travel: Roche, Bristol Myers-Squibb, AstraZeneca. G. Giaccone: Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Institutional, Research Grant: Karyopharm. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono;Financial Interests, Personal, Invited Speaker, Independent member: Grifols;Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc;Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica);Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO;Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer);Non-Fina cial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). All other authors have declared no conflicts of interest.

Three-years real-world evidence of adjuvant dabrafenib plus trametinib (DT) in patients with resected melanoma in Spain (GEM 1901 - DESCRIBE-AD)

Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range: 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI: 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI: 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement: We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study: Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure: P. Cerezuela-Fuentes: Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure: BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal: Financial Interests, Personal, Other, Lecture fees: Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees: Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation: ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales: Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings: BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role: Novartis. J. Medina Martinez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós: Financial Interests, Personal, Other, speaker, consultancy and advisory: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials: Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño: Non-Financial Interests, Advisory Role: Bristol, MSD, Novartis. T. Puértolas: Financial Interests, Personal, Invited Speaker, Speaker and advisory role: BMS, Novartis;Financial Interests, Personal, Invited Speaker: Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role: Pierre-Fabre;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Institutional, Other, Clinical trial: Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions: Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal: GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate: SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel: Financial Interests, Personal, Invited Speaker, Public speaking: Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos: Financial Interests, Personal, Other, Speaker or advisory role: Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role: AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa: Financial Interests, Personal, Advisory Role, Advisory: BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities: Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities: Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation: Roche;Non-Financial Interests, Personal, Member, Vicepresident: Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking: Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials: BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font: Financial Interests, Personal, Full or part-time Employment: Novartis. G. Belaustegui Ferrández: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.

Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study

Background: CSCC is highly immune-responsive;a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC. Methods: Pts received cemiplimab 350 mg IV q3W for up to 4 doses before surgery. The primary endpoint was pCR rate per independent central pathologic review (ICPR). Key secondary endpoints included MPR rate per ICPR, objective response rate (ORR;complete response [CR] + partial response [PR]) per RECIST v1.1, investigator-assessed pCR and MPR, safety and tolerability. Results: At data cutoff date of 01 Dec 2021, 79 pts were enrolled (67 male;median age 73.0 yrs [range, 66.0–81.0];ECOG performance status 0 (n=60) and 1 (n=19) with stage II (n=5), III (n=38), or IV(M0) (n =36) disease;62 pts received all 4 doses (median number of doses given (Q1:Q3), 4 (4:4);70 pts underwent surgery. The study met its primary endpoint: pCR was observed in 40 (50.6%) pts (95% confidence interval [CI], 39.1–62.1%). MPR was observed in an additional 10 (12.7%) pts (95% CI, 6.2–22.0%). ORR was 68.4% (95% CI, 56.9–78.4) (5 CR, 49 PR, 16 stable disease, 8 progressive disease (PD), 1 non evaluable. Reasons 9 pts did not have surgery: 3 responders declined surgery, 2 lost to follow-up or noncompliance, 2 had inoperable PD, 2 due to AE. Fourteen (17.7%) pts experienced Grade ≥3 AE. Four pts died due to AEs: 1 exacerbation of cardiac failure, 2 myocardial infarctions, and 1 COVID-19 pneumonia. The most common AEs regardless of attribution (all grades) were fatigue (30.4%), rash maculo-papular (13.9%), diarrhea (13.9%) and nausea (13.9%). Conclusions: The pCR + MPR of 63.3% by ICPR in pts with Stage II–IV (M0) CSCC is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type. The safety profile of neoadjuvant cemiplimab is consistent with previous anti-PD-1 monotherapy experience. Ongoing follow-up will describe disease-free survival. Clinical trial identification: NCT04154943. Editorial acknowledgement: Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure: N. Gross: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Board: PDS Biotechnology, Shattuck Labs and Genzyme;Financial Interests, Personal, Advisory Role: PDS Biotechnology, Shattuck Labs and Genzyme. D.M. Miller: Financial Interests, Personal, Advisory Role: Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron, Sanofi Genzyme;Financial Interests, Personal, Ownership Interest: Checkpoint Therapeutics;Financial Interests, Personal, Research Grant: Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N. Khushanlani: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, HUYA Bioscience International, Merck, Novartis, GlaxoSmithKline, Celgene, Amgen;Financial Interests, Personal, Advisory Board: EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array Biopharma, Jounce Therapeutics, Immunocore, Bristol Myers Squibb, HUYA Bioscience International;Financial Interests, Personal, Other, honoraria: Sanofi;Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals, Mazor Robotics, Amarin, Transenetrix. V. Divi: Financial Interests, Institutional, Research Grant: Genentech. E.S. Ruiz: Financial Interests, Personal, Advisory Board: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Int rests, Personal, Advisory Role, consulting fees: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Interests, Personal, Member of the Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Other, Advisory board and consulting fees: Bristol Myers-Squibb, Eisai, Genentech, Immunocore, Instil Bio, MacroGenics, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, OncoSec, Pfizer, Rain Therapeutics, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck, Regeneron. F. Meier: Financial Interests, Personal, Other, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and Sanofi;Financial Interests, Personal, Research Grant: Novartis and Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer;Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar Therapeutics, Regeneron Pharmaceuticals. J.L. Atlas: Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol Myers Squibb. J.L. Geiger: Financial Interests, Institutional, Research Grant: Alkermes, Debio, Merck, Regeneron Pharmaceuticals, Inc., and Roche/Genentech;Financial Interests, Personal, Advisory Role: Exelixis, Merck and Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche;Financial Interests, Institutional, Other, Institutional grants and consultancy fees: EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Role: OncoSec Medical. J.H. Choe: Financial Interests, Personal, Advisory Role: Exelixis, Coherus Biosciences, Regeneron Pharmaceuticals, Inc. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche;Financial Interests, Institutional, Research Grant: Amgen. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. K. Fenech: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. H. Han: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb. All other authors have declared no conflicts of interest.

Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study

Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy;and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Results: 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached;estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusions: Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification: NCT02715284. Editorial acknowledgement: Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: A.V. Tinker: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca;Financial Interests, Personal, Other: AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK;Financial Interests, Personal, Other: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners;Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray;Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro;Financial Interests, Personal, Other: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai;Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche;Non-Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline;Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline;Financial Interests, Institutional, Funding: Abbv e, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics;Financial Interests, Personal, Advisory Board: IMAB biopharma. D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp;Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI);Financial Interests, Personal, Other: Myriad Genetics, Tarveda. V. Boni: Financial Interests, Personal, Advisory Board: OncoArt, Guidepoint Global;Financial Interests, Personal, Speaker’s Bureau: Solti;Financial Interests, Personal, Other: START, Loxo, IDEAYA Biosciences;Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina: Financial Interests, Personal, Other: Gentili, Pfizer. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna;Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview;Financial Interests, Personal, Stocks/Shares: PerciHealth;Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro;Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem;Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca;Non-Financial Interests, Advisory Role: Epsilogen;Non-Financial Interests, Other, Member of membership committee: ESGO;Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity;Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. R. Miller: Financial Interests, Personal, Other: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline;Financial Interests, Personal, Speaker’s Bureau: AZD, Clovis Oncology, GSK, Roche. J. Pikiel: Financial Interests, Personal, Other: Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab;Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm;Financial Interests, Personal, Stocks/Shares: Karyopharm;Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen;Financial Interests, Institutional, Invited Speaker: Deciphera;Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. G. Antony: Financial Interests, Personal, Fu l or part-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,;Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche;Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb;Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO;Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG;Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO;Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG.

Synergistic anti-tumor effect of Allocetra-OTS in combination with immune checkpoint inhibitors (ICI)/chemotherapy/CAR T, through in-vivo reprogramming of macrophages

Background: ICI revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Here we investigated the anti-tumoral effect of Allocetra—OTS cellular therapy, in solid tumor models. Methods: Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis.Balb/c mice were inoculated in the peritoneal cavity with AB12 (mesothelioma) stably transduced with pLenti-PGK-V5-Luc-Neo for IVIS visualization and treated with anti-CTLA4, anti-PD1, or cisplatin, with or without Allocetra-OTS (also administered as monotherapy). Kaplan-Meier log rank test was done for survival. CAR T model was induced in SCID-Bg mice were inoculated intraperitoneally with human HeLa-CD19, followed by treatment with 10×109 cells of Allocetra-OTS or vehicle, and 1×107 CD19-CAR T cells or mock T cells. Results: Anti-CTLA4 therapy significantly improved survival from mean 34±9 to 44.9 ±20 days (p<0.05). However, Allocetra-OTS monotherapy improved survival to 52.3 ±20 days (p<0.02) and anti-CTLA4 + Allocetra-OTS combination therapy to 86.7±20 days (p<0.0001) with complete cancer remission in 60-100% of mice. Similar results were seen in combination therapy with either anti-PD1 or cisplatin. In the CAR-T model, SCID-Bg mice survived 30±5 days (range 27–37) and were sacrificed or died from tumor progression. Results were verified using IVIS of intraperitoneal HeLaCD19-Luc cells. CAR T cell therapy significantly improved survival to 55±11 days (p < 0.05 vs MOCK) but Alloctra-OTS further improved survival to 75±10 (p < 0.001) with 20-40% complete remission. Conclusions: During intraperitoneal tumor progression, Allocetra-OTS as monotherapy or in combination with ICI, cisplatin or CAR-T therapy, significantly reduced tumor size and resulted in complete remission in up to100% treated mice. Based on excellent safety profile in > 40 patients treated in prior clinical trials for sepsis and COVID-19, phase I/II clinical trial of Allocetra-OTS plus chemotherapy is planned for Q3 2022, and a second phase I/II clinical trial of Allocetra-OTS plus anti-PD1, as a second- and third-line therapy in various cancers, is planned for Q4 2022. Legal entity responsible for the study: The authors. Funding: Enlivex Therapeutics Ltd. Disclosure: D. Mevorach: Financial Interests, Personal, Royalties, Founder & CSO: Enlivex Therapeutics LTD. E. Yalon, E. Regev, C. Ankri, O. Hershkovitz, Y. Shabat, B. Reicher: Financial Interests, Personal, Full or part-time Employment: Enlivex Therapeutics LTD.

Niraparib plus aromatase inhibitors (AI) for germinal mutated BRCA1/2 (gBRCAm) or homologous recombination-deficient (HRd), hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC): LUZERN interim analysis

Background: The poly(ADP-ribose) polymerase inhibitor niraparib showed clinical activity in advanced gBRCAm ovarian and breast cancers. LUZERN aims to assess the effectiveness of niraparib plus AI in HR+/HER2–, AI-resistant ABC with a pathogenic variant in homologous recombination-related genes. Here we report findings from the stage 1 interim analysis. Methods: This open-label, single-arm, Simon’s 2-stage, phase II trial is enrolling HR+/HER2– ABC patients (pts) with gBRCAm (cohort A;n=6 in stage 1, n=7 in stage 2) and gBRCA wild-type/HRd (cohort B;n=9 in stage 2). Pts had to have received ≤1 prior line of chemotherapy for ABC, 1–2 prior lines of endocrine therapy for early or ABC with secondary endocrine resistance to the last AI regimen. Pts receive niraparib (200/300mg daily orally) plus AI (same agent given with the prior regimen) on each 28-day cycle. Primary endpoint: clinical benefit rate (CBR) as per RECIST 1.1. Secondary endpoints: overall response rate, progression-free survival (PFS), and safety per CTCAE 5.0. If ≥1/6 pts experienced clinical benefit, the trial should proceed to stage 2. Results: Six pts were enrolled in stage 1. Median age was 46 years (range 32–76), 66.7% of pts had visceral disease, and 83.3% had received prior CDK4/6 inhibitor-containing regimen for ABC. At data cut-off, 50.0% of pts were ongoing and median duration of treatment was 4.6 months (range 2.4–5.7). One patient achieved complete response, meeting the criterion to proceed to stage 2. Median investigator-assessed PFS was 5.3 months (95%CI 3.9–NA). The most frequent adverse events (AEs) of any grade (G) were nausea (3 [50.0%]), neutropenia (2 [33.3%];16.7% G3), constipation (2 [33.3%]), and vomiting (1 [16.7%]). Serious AEs occurred in 3 pts (50.0%;G3 COVID-19 pneumonia;G3 pseudomonal bacteriemia;G2 sacral pain). No treatment-related discontinuations/deaths were reported. Conclusions: Niraparib plus AI showed preliminary activity with a tolerable safety profile in gBRCAm HR+/HER2– AI-resistant ABC pts. Based on the steering committee recommendation, enrolment in cohorts A and B is ongoing. Clinical trial identification: ClinicalTrials.gov identifier: NCT04240106. Legal entity responsible for the study: MEDSIR. Funding: GlaxoSmithKline. Disclosure: J.Á. García Saenz: Financial Interests, Personal, Advisory Board: Seagen, Gilead;Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD, Exact Sciences;Financial Interests, Institutional, Funding: AstraZeneca. J. De la Haba Rodriguez: Financial Interests, Personal, Other, Consultant and Advisory Role, Research Funding and Speaking: Pfizer, Novartis, Roche, Lilly;Financial Interests, Personal, Other, grant support: Pfizer. J.E. Ales Martínez: Financial Interests, Personal, Other, travel grant: Pfizer;Financial Interests, Personal, Research Grant: MEDSIR. E. Alba Conejo: Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, BMS, Astrazeneca, Pierre Fabre, Daiichi, Exact Sciences;Financial Interests, Personal, Research Grant: Pfizer. J. Balmaña: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer;Financial Interests, Institutional, Other, Steering committee member: AstraZeneca;Financial Interests, Institutional, Principal Investigator: Medsir, Pfizer. J.M. Perez Garcia: Financial Interests, Personal, Advisory Role: Lilly,Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Medsir;Financial Interests, Personal, Other, travel expenses: Roche. M. Sampayo-Cordero: Financial Interests, Personal, Other, honoraria: Medsir, Syntax for Science, Optimapharm, and Ability pharma;Financial Interests, Personal, Research Grant: Medsir;Financial Interests, Personal, Other, travel expenses: Medsir, Syntax for Science, Optimapharm, and Roche;Financial Interests, Personal, Other, consultant: Medsir, Syntax for Science, and Optimapharm;Financial Interests, Personal, Speaker’s Bureau: Medsir;Financial Interests, Personal, Full or part-time Employment: Me sir. A. Malfettone: Non-Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks;Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.;Financial Interests, Personal, Stocks/Shares: MEDSIR, Nektar Pharmaceuticals, Leuko (relative);Financial Interests, Personal, Other, travel, accomodation: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD;Financial Interests, Personal, Stocks/Shares: MEDSIR and Initia-Research;Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK;Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, and MSD;Financial Interests, Personal, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, and Agendia;Financial Interests, Personal, Other, travel compensation: Roche, Lilly, Novartis, Pfizer, and AstraZeneca. All other authors have declared no conflicts of interest.

Factors associated with increased financial toxicity after the completion of radiation treatment for gynecologic cancer (512)

Objectives: Financial toxicity (FT) impacts approximately 50% of patients with gynecologic malignancies. Still, little is known about factors that predispose patients receiving radiation therapy to financial distress or what impact the COVID-19 pandemic had on their financial well-being. We evaluated FT in patients with gynecologic cancer treated with radiation before and after the start of the COVID- 19 pandemic. Methods: Patients from an urban, academic gynecologic radiation oncology practice completed a survey one month after completing radiation from August 2019-March 2020 and November 2020-June 2021. The survey included demographic questions, the Comprehensive Score for Financial Toxicity (COST) tool, and the EQ-5D to measure the quality of life (QOL). Pandemic-related questions were added during the second survey period (pandemic cohort). As with our prior work, high FT was defined as a COST score of ≤23. We assessed the correlation of COST scores with QOL. We used logbinomial regression to examine associations between FT and costcoping strategies, adjusting for age and insurance. Results: Of 97 respondents (92% response rate), 49% completed the survey before, and 51% completed it after the pandemic started. Among the participants, 76% identified as White, 11% as Black, and 8% as Asian. Most patients had uterine (64%), followed by cervical (24%) and vaginal (6%) cancer. Two-thirds (60%) received external beam radiation with or without brachytherapy;the remaining 40% had brachytherapy alone. The median COST score was 15 (IQR: 7-19) in the high FT group (n=27) and 33 (IQR: 28-36) in the low FT group (n=70). High FT correlated with worse QOL (r=-0.37, p<0.01) and was associated with younger age and type of insurance (both p <0.03). Patients with high FT were more likely to move from full- to parttime employment (22% vs 1%, p<0.01), six (95% CI: 1.0-36) times more likely to delay/avoid medical care, 14 (95% CI: 3-64) times more likely to borrow money, and seven (95% CI: 2-27) times as likely to reduce spending on basic goods. Patients with high FT were more likely to report that decreased ability to work (48% vs 13%), medical bills (41% vs 13%), and transportation or parking (15% vs 3%) mostly contributed to their financial stress (p<0.05 for all). The pandemic cohort had fewer patients with high FT than the pre-pandemic cohort (20% vs 35%, p=0.10) and a higher median COST score (32 [IQR: 25-35] vs 27 [IQR: 19-34], p=0.07). The use of cost-coping strategies did not differ between cohorts. Conclusions: Privately insured, younger patients who received radiation for gynecologic cancer were at risk for FT. High FT correlated with worse QOL and was associated with delays or avoidance of medical care and other cost-coping strategies. The prevalence of high FT was not statistically different before and during the pandemic, though we observed less FT in the pandemic cohort. More work is needed regarding the impact of the COVID-19 pandemic on the financial well-being of patients with cancer.

Primary analysis of MOUNTAINEER: A phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC

Background: Despite the occurrence of HER2 amplification/overexpression (HER2+) in ~3% to 5% of all patients with metastatic colorectal cancer (mCRC) and up to ~10% of patients with RAS/BRAF wild-type mCRC, there are currently no FDA- or EMA-approved HER2-directed therapies for HER2+ mCRC. Patients with mCRC who progress on early lines of chemotherapy regimens receive limited clinical benefit from current standard-of-care treatments. Tucatinib is a highly selective, HER2-directed, tyrosine kinase inhibitor. The MOUNTAINEER trial (NCT03043313) was initiated to evaluate the efficacy and safety of the investigational combination of tucatinib with trastuzumab in patients with HER2+ mCRC. Here we present results from the primary analysis of MOUNTAINEER. Methods: MOUNTAINEER is a multi-center, open-label, randomised, phase 2 trial conducted in the US and Europe. Eligible patients had HER2+ (one or more local tests: 3+ immunohistochemistry, 2+ immunohistochemistry with amplification by in situ hybridization, or amplification by next‑generation sequencing of tumor tissue) and RAS wild-type mCRC with progression on or intolerance to fluoropyrimidine, oxaliplatin, irinotecan, and an anti-VEGF antibody. Measurable disease and an ECOG performance status of 0–2 were required. Previous HER2-directed therapies were not permitted. The trial initially consisted of a single cohort (Cohort A) to be treated with tucatinib (300 mg PO BID) and trastuzumab (8 mg/kg IV then 6 mg/kg IV every 3 weeks). The trial was expanded to include patients randomised 4:3 to receive tucatinib + trastuzumab (Cohort B) or tucatinib monotherapy (Cohort C). The primary endpoint is confirmed objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) in Cohorts A+B. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results: MOUNTAINEER enrolled 117 patients between 08Aug2017 and 22Sept2021. Data cutoff was 28Mar2022. The median age was 56.0 years (range, 24, 77), and baseline characteristics were balanced across cohorts. Eighty-six patients received at least 1 dose of study treatment in Cohorts A+B, and 30 patients received tucatinib monotherapy in Cohort C (total, 116). The overall median duration of follow-up was 16.3 months (IQR, 10.8, 28.2). In Cohorts A+B, the confirmed ORR by BICR was 38.1% (95% CI, 27.7, 49.3). The median DOR was 12.4 months (95% CI, 8.5, 20.5). The median PFS was 8.2 months (95% CI, 4.2, 10.3), and the median OS was 24.1 months (95% CI, 20.3, 36.7). The most common adverse events (AEs) in Cohorts A+B were diarrhoea (64.0%), fatigue (44.2%), nausea (34.9%), and infusion-related reaction (20.9%);the most common AE of grade ≥3 was hypertension (7.0%). Adverse events leading to tucatinib discontinuation in Cohorts A+B occurred in 5.8% of patients and included alanine amino transferase increase (2.3%), COVID-19 pneumonia (1.2%), cholangitis (1.2%), and fatigue (1.2%). No deaths resulted from AEs. Conclusions: In patients with chemotherapy-refractory HER2+ mCRC, tucatinib in combination with trastuzumab was well tolerated with clinically meaningful antitumor activity including durable responses and a median overall survival of 2 years. Tucatinib in combination with trastuzumab has the potential to become a new standard of care for patients with HER2+ mCRC. Clinical trial identification: NCT03043313. Editorial acknowledgement: The authors thank Joseph Giaconia of MMS Holdings, Michigan, USA for providing medical writing support/editorial support, which was funded by Seagen Inc., Bothell, WA, USA in accordance with Good Publication Practice (GPP3) guidelines. Legal entity responsible for the study: Seagen Inc. Funding: Seagen Inc. Disclosures: J. Strickler: Advisory / Consultancy: Seagen, Bayer, Pfizer;Research grant / Funding (institution): Amgen, Roche/Genentech, Seagen. A. Cercek: Advisory / Consultancy: Bayer, Merck, Seagen;Research grant / Funding (institution): Seagen, GSK, Rgenix. T. André: Honoraria (self : Amgen, Astra-Zeneca, Bristol-Myers Squibb, Gritstone Oncology, GlaxoSmithKline, Haliodx, Kaleido Biosciences, Merck & Co., Inc., Pierre Fabre, Sanofi, Servier, Merck & Co., Inc, Servier;Advisory / Consultancy: Astellas Pharma, BMS, Gritstone Oncology, Transgène, Roche/Ventana, Seagen, Merck & Co., Inc, Servier;Research grant / Funding (institution): BMS, Seagen, GSK;Travel / Accommodation / Expenses: BMS, Merck & Co., Inc. K. Ng: Advisory / Consultancy: Seattle Genetics, Bicara Therapeutics, GlaxoSmithKline;Research grant / Funding (institution): Pharmavite, Evergrande Group, Janssen. E. Van Cutsem: Advisory / Consultancy: AbbVie, Array, Astellas, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Helsinn, Incyte, Ipsen, Janssen Research, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Pierre Fabre, Roche, Seattle Genetics, Servier, Sirtex, Terumo, Taiho, TRIGR, Zymeworks;Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. C. Wu: Research grant / Funding (institution): Seagen. A. Paulson: Research grant / Funding (institution): Seattle Genetics. J. Hubbard: Research grant / Funding (institution): Seattle Genetics. H. Lenz: Honoraria (self): BMS, Bayer, Roche;Advisory / Consultancy: Bayer, Merck, Roche;Travel / Accommodation / Expenses: BMS, Bayer, Merck KG;Shareholder / Stockholder / Stock options: Fulgent. M. Stecher: Full / Part-time employment: SeaGen. W. Feng: Full / Part-time employment: Seagen. T. Bekaii-Saab: Honoraria (self): Royalties: Uptodate;Advisory / Consultancy: Consulting (to institution): Ipsen, Arcus, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, Eisai and Merck., Consulting (to self): Stemline, AbbVie, Boehringer Ingelheim, Janssen, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Kanaph, Astra Zeneca, Deciphera, MJH Life Sciences, Aptitude Health, Illumina and Foundation Medicine, IDMC/DSMB: Fibrogen, Suzhou Kintor, Astra Zeneca, Exelixis, Merck/Eisai, PanCan and 1Globe;Research grant / Funding (institution): Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Eisai, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, BMS.;Licensing / Royalties: WO/2018/183488: HUMAN PD1 PEPTIDE VACCINES AND USES THEREOF – Licensed to Imugene, WO/2019/055687: METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER CACHEXIA – Licensed to Recursion. All other authors have declared no conflicts of interest.

Real-time genotyping-based breast cancer risk assessment in MyPeBS, an international randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS)

Background: Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach. Methods: MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants. Results: As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer;72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality;and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks). Conclusions: Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants. Clinical trial identification: NCT03672331. Legal entity responsible for the study: Unicancer. Funding: European Commission and French National Cancer Institute. Disclosure: S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Exact Sciences;Financial Interests, Institutional, Advisory Board: Novartis;Financial Interests, Institutional, Advisory Board: Pierre fabre;Financial Interests, Institutional, Advisory Board: Orion;Financial Interests, Institutional, Advisory Board: Sanofi;Financial Interests, Institutional, Advisory Board: Rappta;Financial Interests, Institutional, Advisory Board: Cellectis;Financial Interests, Institutional, Advisory Board: Isis/servier;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Seagen;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: MSD;Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare;Financial Interests, Institutional, Invited Speaker: Roche Genentech;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Puma;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Orion;Financial Interests, Institutional, Invited Speaker: Sanofi;Financial Interests, Institutional, Funding: GE;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho;Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife;Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI;Financial Interests, Personal, Advisory Role: Amaris;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Sensorion;Financial Interests, Personal, Advisory Role: Biophytis;Financial Interests, Personal, Advisory Role: Servier;Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.

Occupational health for migrant workers in Spain, why does it matter?

Spain is the fourth country with the largest number of immigrants in Europe, resulting in a large proportion of migrant workers. Women constitute 48% of international migrants who suffer poor working conditions linked to the positions they mainly occupy within certain fields such as the domestic sector and caregiving services. In this connection, Spain is the second country in Europe with the highest number of domestic workers (619,600 people). In addition, 95% of caregivers in Spain are Latin American women. It also should be noted that during the COVID-19 pandemic, women have been the most affected, making up 54.8% of the total infected. They have been frequently working under unsafe and hazardous OHS conditions, often without the necessary personal protective equipment (PPE) and many being exposed to significant risks due to their direct personal contact with patients with COVID-19. To date, many researchers have examined the working conditions of immigrants in Spain who are known to have to deal with adverse working conditions. The main objective of this research is to investigate the patterns of work and working conditions of immigrants living in Spain and to understand how these factors may affect their health. Many of our results have showed: In general, four employment sectors were most commonly occupied by these immigrants, including caregiving and food service for women and agriculture and construction for men. Most immigrants were from Latin America, either unemployed or working part-time jobs, and not hired under an employment contract. Most worked in low-qualified jobs, and were exposed to occupational hazards such as falls from heights, manual handling of materials, and psychological strain. The lack of training on occupational risk prevention and labour rights were related to a low identification of work-related situations leading to a negative impact on the health of immigrants. In caregiving sector (mainly occupied by women) the main risks identified were biological risks, physical attacks, falls, wounds and musculoskeletal complaints related to handling patients and carrying out household chores. Most of them had not taken an occupational health test and did not report accidents occurring in the workplace for fear of losing their jobs. The main health problems were related to physical and mental health (such as musculoskeletal diseases and stress). During the current COVID 19 pandemic, women have been the main providers of care and domestic work in the homes where they have been confined, renouncing their own freedom of movement and social interaction. They have been responsible of all the domestic work, resulting in non-stop working days during the lockdown.