Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

Magseed wide local excisions - The first 50

Introduction: Prior to 2021, impalpable tumours in our unit were localised with Somatex wires. During the COVID pandemic we introduced Magseed due to its logistical advantages in allowing surgery on a site distant from our breast unit. We wanted to ensure our clinical outcomes with this new system were equivalent to those using wire localisation. Method(s): Electronic records for the first 50 consecutive Magseed localised wide local excisions and the preceding 50 consecutive wire localised wide local excisions were compared. Excision biopsies, palpable lesions, bracketed lesions and post neoadjuvant treatment patients were excluded. Patient demographics, tumour size, inadequate radial margin involvement rate, reoperation rate for margins, specimen weight, number of cavity shaves and operative time were recorded. [Formula presented] Results: Results are shown in table 1. There were no preoperative differences in the two groups. There were no significant differences in outcomes between the two groups, with a trend towards lower margin involvement rates but more shaves in the Magseed group. The mean operative time was slightly shorter in the Magseed group despite more axillary procedures being performed in this group. Conclusion(s): The change to the Magseed system led to logistical advantages with patient outcomes at least equivalent to wire guided excision.Copyright © 2023

Imperial Prostate-4 Comparative Healthcare Research Outcomes of Novel Surgery in Prostate Cancer (Ip4-Chronos): Early Feasibility, Safety and Functional Outcomes from a Pilot Rct

INTRODUCTION AND OBJECTIVE: Randomised comparative outcomes are unavailable for focal therapy in localised prostate cancer. IP4 CHRONOS is an RCT aimed to optimise recruitment of patients dependent upon clinician and patient equipoise. METHOD(S): Patients with clinically significant localised prostate cancer could opt for IP4-CHRONOS-A or IP4-CHRONOS-B. IP4- CHRONOS-A randomised patients 1:1 between focal therapy(HIFU or cryotherapy) versus radical therapy(radiation or prostatectomy). Using a multi-arm-multistage(MAMS)design, IP4-CHRONOS-B randomised between focal alone(FTA) and focal combined with neoadjuvant medication (12 weeks of finasteride [FTF] or bicalutamide [FTB]). We report the pilot phase outcomes on feasibility of randomisation, early safety outcomes relative to treatment and genito-urinary functional outcomes following over 12 months treatment in IP4-CHRONOS-B. IP4-CHRONOS had ethics committee approval and was registered(ISRCTN17796995). RESULT(S): Following COVID-19 adjustments, IP4-CHRONOSA did not meet its feasibility target. Having randomised 36 patients via10 sites with a recruitment rate (95% CI) of 18% (13-23) & randomisation rate of 97%(86-100). IP4-CHRONOS-B did meet its target, randomising 64 patients across 7 sites with a recruitment rate of 43% (35-52) &randomisation rate of 100%(94-100). The only patients to withdraw were randomised to the radical arm of IP4-CHRONOS-A(4 [22%]) All patients in IP4-CHRONOS-B were compliant with neoadjuvant treatment.Only 1 patient reported CTCAE V4.0 grade>=3 adverse event(AE) in IP4-CHRONOS-A following radical treatment, another patient in each arm reported a serious adverse event(SAE) following treatment. 1 &3 patients reported an AE &SAE following FTB. 2 and 3 patients reported an AE &SAE following FTA. No patients reported any AE or SAE event following FTF. Figure 1 demonstrates generally well preserved genito-urinary function following focal treatment+/-neoadjuvant treatment. CONCLUSION(S): IP4-CHRONOS evaluated patient and physician equipoise regarding focal therapy. Traditional randomisation was not feasible due to strong patient preferences, while a MAMS RCT investigating the role of neoadjuvant agents combined with focal therapy was.

Extended Neoadjuvant Chemotherapy in Delayed Primary Resection of Ewing Sarcoma During the COVID-19 Era: A Case Report

CASE: A 13-year-old adolescent boy visited our hospital with a growing mass on his left leg. Investigations and examinations were performed to obtain a final diagnosis of Ewing sarcoma in the head of the left fibula with lung metastasis. Neoadjuvant chemotherapy was extended to 11 courses with radiation before wide tumor resection could be performed. The final 3 adjuvant chemotherapy courses were administered to complete the original protocol while surgical resection complications were also treated. The pathological report revealed free margin resection with nonviable tumor cells. CONCLUSION: An extended neoadjuvant chemotherapy regimen with additional radiation therapy for Ewing sarcoma provided extra local control and allowed limb salvage. Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.

Predictors, surrogate and patient-reported outcomes in neoadjuvant immunotherapy for lung cancer: A single-center retrospective study

Background Development of immunotherapy/molecular targeted therapy has significantly increased survival/QoL in advanced stages of NSCLC. Aim(s): to analyze outcome predictors, surrogate outcomes, and PROMs after neoadjuvant immunotherapy for initially unresectable NSCLC. Methods Initially unresectable NSCLC (2014-2021) patients who received immunotherapy +/- platinum-based chemo and/or radiotherapy evaluated after response (reduction of primary tumor and/or mediastinal lymphadenopathy/control of distant metastatic disease underwent surgical resection). PROMs were recorded using EORTC QLQ-29. Results 19 underwent salvage surgery after ICI. 14 had partial response (73.6%), 5 stable disease. Diagnosis was achieved by endobronchial ultrasound (EBUS) in 8 (42.1%), fine-needle aspiration biopsy (FNAB) in 7 (36.8%), metastasis biopsy in 4 (21.0%). 11 (57.9%) were treated with neoadjuvant platinum-based chemo before or with ICI, 1 (5.2%) pemetrexed before ICI, 5 (26.3%) radiotherapy for metastatic control. 3 (15.7%) had ICI adverse effects. Radiotherapy was never used preoperatively for pulmonary/mediastinal disease. 7 (36.8%) received adjuvant therapy (5 [26.3%] pembrolizumab, 1 [5.2%] pemetrexed, 1 [5.2%] pemetrexed + pembrolizumab). 4 (21.0%) had local relapse (no systemic relapse). Median OS was 19 months (range: 2-57.4). At 2 months, 94.7% were alive (6 months: 89.5%;31 months: 79.5%). 2 (10.5%) had local recurrence. 2 (10.5%) died due to recurrence, 1 (5.2%) to COVID. 4 (21.0%) relapsed (median DFS: 5.3 months [range: 2.2-13.0]). PROMs were reviewed retrospectively at 30 days/1 year with significant decrease in coughing, side effects of treatment, surgery-related problems. [Formula presented] Conclusions Radical surgical resections following definitive immunotherapy/immune-chemotherapy in selected initially unresectable NSCLC are feasible and safe (low surgical-related mortality and morbidity). Symptoms and surgery-related outcomes were lower with higher QoL due to a selected group of highly motivated patients. Legal entity responsible for the study The authors. Funding Ministero della Salute. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

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.

PD11-04 Primary results of SOLTI-1503 PROMETEO phase 2 trial of Combination of Talimogene Laherparepvec (T-VEC) with Atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy

Background: Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2- negative breast cancer (BC) remains an unmet medical need. However, no therapies to date have tested their activity directly in chemo-resistant RD. Here, we hypothesized that combining an oncolytic virus such as T-VEC with atezolizumab may offer clinical benefit in patients (pts) with RD after standard NAC. To our knowledge, PROMETEO is the first trial that examines the activity of immunotherapy in pts with RD prior to surgery. Method(s): PROMETEO (NCT03802604) is a singlearm, open-label, multicenter phase II trial. Women with triple-negative BC (TNBC) or hormone receptor-positive/HER2-negative (HR+/HER2-) BC with baseline (i.e., before NAC) ki67 >= 20% were eligible. RD was confirmed with a magnetic resonance imaging (MRI) showing a tumor diameter >= 10 mm and a core-biopsy detecting the presence of invasive cells. Before surgery, T-VEC was administered intratumorally on week 1 (106 pfu/mL), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) was administered intravenously every 2 weeks for 4 infusions, starting at week 4. Surgery was performed in < 3 weeks after completing the treatment. The primary objective was to evaluate the efficacy of the combination, measured by the rate of residual cancer burden (RCB) class 0/1 at surgery. Tumor samples collected at 5 timepoints (before NAC, during screening period, after first dose of T-VEC, after first dose of T-VEC and atezolizumab and at surgery) were mandatory to assess gene expression, tumor-infiltrating lymphocytes (TILs), immune cells PD-L1 IHC (SP142), tumor mutational burden (TMB) by FoundationOne and other translational endpoints. Result(s): Between Dec 2018 to Feb 2022, 28 pts were enrolled: 20 pts with HR+/HER2- disease and 8 pts with TNBC. Median age was 47 (range 31-71) and 71% of pts were premenopausal. At diagnosis before NAC, clinical stage II disease represented 60.7%, cN+ 60.7%, median Ki-67 was 37.5% (range 20%-95%), high TILs (>=10%) 37%, median TMB was 3 (0-19) and only 1 of 27 pts (3.7%) had a PD-L1-positive tumor. After NAC, mean tumor size by MRI was 28.3 mm (10-93). Two pts discontinued from the trial (1 withdrawal of consent and 1 COVID infection). The completion of 5 cycles of treatment was achieved by 73% of pts. The overall RCB-0/1 rate was 25% (7 of 28, 95% IC 10.7 - 44.9%), all with RCB 0 (pathologic complete response [pCR]). The pCR rate was 30% in HR+/HER2- disease and 12.5 % in TNBC. Radiological response by MRI was achieved by 3 of 28 pts (10.7%). Interestingly, none of the 7 pts with a pCR had radiological response (stable disease n=5, progressive disease [PD] n=2). Six pts (21.4%) had radiological PD and had RCB 2/3. Overall, 27 (96%) patients had at least one treatment-emergent adverse event (TEAE) of any grade. Most common grade 1 or 2 AEs were fever (11 pts, 39.3%), ALT increased (9 pts, 32.1%), AST increased (8 pts, 28.6%), arthralgia (6 pts, 21.4%) and anemia (6 pts, 21.4%). Grade 3 reversible neutropenia occurred in 1 patient. Across all pts, significant increases (p< 0.001) in TILs, immune genes and immune PDL1+ cells were observed after 1 dose of TVEC, 1 dose of the combination and at surgery. Intrinsic subtype changes at surgery occurred in 73.1% of cases, mostly (46.1%) Luminal A/B converting to Normal-like. At surgery, 19 of 26 (73.1%) of tumors were PDL1+. Conclusion(s): Two months of T-VEC in combination with atezolizumab induced a pCR in a subgroup of pts with chemoresistant HER2- breast cancer. This effect is probably related to the immune activation provoked by the combined treatment. Interestingly, a high discrepancy was observed between the presurgical radiological imaging and the actual surgical pathological report. Pre-operative window-ofopportunity trials in this context might provide important clues regarding the activity of novel treatment strategies.

A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future

Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Method(s): We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Result(s): Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/ etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1+/-10+/-9/L vs 2.90+/-10+/-9/L, p<0.0001);and neutropenia rates were markedly lower (2% vs. 93%, P=,0.0001). Hospital admission rates were significantly lower in G-CSF users compared to nonusers (19% vs. 69%, P,0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusion(s): During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.

Change in breast cancer detection method, stage at diagnosis and treatment during the COVID19 Pandemic: 2019-2021

Objective: Identify changes in breast cancer detection method, stage at diagnosis and treatment prior to, during and after stay-at-home orders and restricted health care access due to COVID-19. Method(s): Statistical comparison of detection method (patient (PtD), mammography (MamD) or other), Anatomic TNM Stage 8 (0-IV) and invasive BC treatment change over time by three time periods (time 1: 2019+Q1 2020;time 2: Q2-Q4 2020;time 3: 2021) using chi-square analysis in an institutional retrospective cohort of first primary breast cancer (BC) patients (n=1799), years 20192021. Result(s): In the years prior to the study, 2016-2019, there was no difference in detection method or stage at diagnosis by year with 682 to 733 newly diagnosed BC annually (p=.462). In 2020 (n=535) and 2021 (n=582) annual diagnosed cases dropped 22% and 15% from 2019 levels. Compared to time 1, time 2 MamD BC dropped significantly (64% to 58%) with a subsequent increase in MamD BC to 70% in time 3 (p < .001) creating a U-shaped curve for MamD over time. PtD BC increased in time 2 from 30% to 36% but declined in time 3 to 25% (p <.001). Concurrently, stage at diagnosis shifted from time 1 to time 2 with stage 0 and I declining [stage 0: 21% to 16%, stage I: 40% to 38%] and stage II and IV increasing [stage II: 28% to 33%, stage IV: 2% to 4% stage IV] (p<.001). Subsequently in 2021 stage shifted again with an increase in stage 0 to 22% and stage I to 45% and a decline in stage II (33% to 24%), III (9% to 7%) and IV (4% to 2%) (p<.001). Combining stage 0 and I, the percentage of lower stage BC declined from 61% to 54% and increased to 67% in time 3 (2021) when health services became more readily accessible. There was no change in type of surgery for invasive breast cancer (stage I-III, n=1386) with equivalent numbers of breast conserving surgery (58%), subcutaneous mastectomy (24%) and mastectomy (18%) over the time period. Chemotherapy treatment rates for invasive BC did not change (38%). Radiation therapy increased from 66% (time 1: 2019+Q1 2020) to 73% (time 2: Q2Q4 2020) then back to 64% in time 3: 2021 (p=.007) independent of surgery type but concordant with an increase in stage IA and stage IIB BC among invasive breast cancer cases in time 2: Q2-Q4 2020 (p<.001). Likewise, neoadjuvant therapy increased and then declined from 33% to 38% to 29% from time 1 to time 3 (p<.001). Conclusion(s): Number of diagnosed BC cases fell after the first quarter of 2020 during the time of COVID-19 related shut downs and decreased access to health services. During the Q2-Q4 2020 time period mammography detected BC declined with a relative increase in patient detected breast cancer. When mammography detection declined, BC stage at diagnosis shifted to higher stage concurrent with increased rates of radiation and neoadjuvant therapy. In 2021, the relative increase in mammography detected BC indicates a return to more normal screening patterns with a catch up for screening lost in the prior year due to access limitations. In the third time period: 2021, with the return to prior levels of mammography detected breast cancer, stage shifted back to pre-pandemic expected distribution and the excess treatment with radiation and neoadjuvant therapy declined to previously observed levels. Although the changes in detection method, stage and treatment did not persist they were statistically significant and could represent a need for re-establishing prepandemic screening behavior. (Table Presented).

Effect of a 12 Week Virtual Supervised Exercise Program on Cardiorespiratory Fitness in Breast Cancer Patients Undergoing Chemotherapy: Results from the STRENGTH Trial

Background: Chemotherapy (CTX) for breast cancer (BC) can have a detrimental effect on cardiorespiratory fitness (CRF), as measured by VO2max. This decline may be attenuated by physical activity, which can also reduce mortality risk and improve quality of life (QoL) for patients (pts) with BC. During the COVID-19 pandemic, many have pivoted to home-based exercise routines, which have been shown to be safe and feasible for pts with BC receiving CTX. We conducted the STRENGTH Trial to evaluate the effect of a 12-week virtual supervised exercise program in BC pts receiving CTX on CRF. Method(s): This is a single-center, prospective, single-arm study designed to evaluate the effect of a 12-week virtual supervised exercise training program on CRF in BC pts receiving CTX. Participants aged >=18 years with stage I-IV BC who were planned to receive at least 12 weeks of CTX of investigator's choice were eligible for inclusion. Participants were asked to complete a total of 150 minutes (min) of moderate intensity physical activity/week, as a combination of a 45 min weekly virtual personal training session and workout classes streamed from the Peloton Digital platform (i.e. walking, running, cardio, yoga, strength training, and cycling). The primary endpoint was the distance walked on a Six-Minute Walk Test (6MWT), an accepted surrogate marker for VO2max, at the start and completion of the program. Secondary endpoints included assessment of QoL using the Functional Assessment of Cancer Therapy - General (FACT-G) and symptom assessment using the MD Anderson Symptom Inventory (MDASI) questionnaires at the beginning, middle and end of the study. Exploratory endpoints included treatment adherence, toxicities, completion and response. Result(s): 33 participants signed consent for the clinical trial and 2 withdrew voluntarily prior to beginning the program. 5 participants discontinued prematurely due to a diagnosis of COVID-19 (N=3) and pulmonary embolism (N=2) and were not included in the primary endpoint. One participant remains on study at this time. Median age 49 yrs;range 33-68. Mean BMI 29.55;range 18.1-46.5. 13 HR+/HER2-, 7 HR-/HER2-, 11 HER2+. 14 (45%) pts had Stage I, 11 (35%) pts had Stage 2, 5 (16%) pts had Stage 3, 1 (3%) pt had Stage 4. 23 pts (70%) received either an anthracycline or HER2-based therapy. 19 pts (61%) received neoadjuvant CTX on study, 11 pts (35%) received adjuvant CTX and 1 pt (3%) received treatment in metastatic setting. The average number of exercise min per week per participant was 123.2 min (95% CI, 104.1-142.2), with a relative dose intensity of 82%. In the pts that completed the study thus far (N=25), there was no statistically significant difference between the distance walked during the 6MWT at the start and end of the study (median difference= -10m, range: -129-150m, p= 0.67). There was no statistically significant difference in the FACT-G score at the start and end of the study (median difference= -1.0, range -17.83- 30.0, p=0.54). Pts scored higher on the MDASI (median difference= 0.33, range -1.55-4.62, p=0.04) at the end of the exercise program compared to the beginning. There were no new or unexpected treatment toxicities observed. Conclusion(s): Pts who participated in a 12-week virtual supervised exercise program during CTX for BC did not experience a statistically significant difference in the distance walked during the 6MWT between the beginning and end of the exercise program. Exercise may attenuate the decline in cardiorespiratory function that has historically been observed with CTX for BC. Some pts were not able to adhere to the recommended 150 min of exercise/week suggesting a potential need for modified exercise targets for pts with BC undergoing CTX. This study is limited by a small sample size and larger, randomized clinical trials are needed to further evaluate optimal exercise recommendations for patients with BC undergoing CTX in order to maintain and potentially, even improve, cardiorespiratory function.

Consequences of anastomotic leaks after minimally invasive esophagectomy: A single-center experience

Background: Anastomotic leak (AL) after minimally invasive esophagectomy (MIE) is a well-described source of morbidity for patients undergoing surgical treatment of esophageal neoplasm. With improved early recognition and endoscopic management techniques, the long-term impact remains unclear. Method(s): A retrospective review was conducted of patients who underwent MIE for esophageal neoplasm between January 2015 and June 2021 at a single institution. Cohorts were stratified by development of AL and subsequent management. Baseline demographics, perioperative data, and post-operative outcomes were examined. Result(s): During this period, 172 MIEs were performed, with 35 of 172 (20.3%) complicated by an AL. Perioperative factors independently associated with AL were post-operative blood transfusion (leak rate 52.9% versus 16.8%;p = 0.0017), incompleteness of anastomotic rings (75.0% vs 19.1%;p = 0.027), and receiving neoadjuvant therapy (18.5% vs 30.8%;p < 0.0001). Inferior short-term outcomes associated with AL included number of esophageal dilations in the first post-operative year (1.40 vs 0.46, p = 0.0397), discharge disposition to a location other than home (22.9% vs 8.8%, p = 0.012), length of hospital stay (17.7 days vs 9.6 days;p = 0.002), and time until jejunostomy tube removal (134 days vs 79 days;p = 0.0023). There was no significant difference in overall survival between patients with or without an AL at 1 year (79% vs 83%) or 5 years (50% vs 47%) (overall log rank p = 0.758). Conclusion(s): In this large single-center series of MIEs, AL was associated with inferior short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, without an accompanying impact on 1-year or 5-year survival. Key message: In this large, single-center series of minimally invasive esophagectomies, anastomotic leak was associated with worse short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, but was not associated with worse long-term survival. The significant association between neoadjuvant therapy and decreased leak rates is difficult to interpret, given the potential for confounding factors, thus careful attention to modifiable pre- and peri-operative patient factors associated with anastomotic leak is warranted.Copyright © 2022 The Authors

Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating longcourse chemoradiation versus short-course radiation therapy

Background: Interest in organ preservation (OP) strategies for rectal cancer (RC) patients persists. The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to OP is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Method(s): During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as alive, TME-free, and with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). Result(s): We identified 563 consecutive patients with RC treated with TNT, of whom 231 were excluded due to either metastatic disease, synchronous/metachronous malignancies, or non-adenocarcinoma histology (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. The cCR rate was numerically higher in patients treated with radiation first, as compared to chemotherapy first (53% vs. 44% (LCRT) and 52% vs. 43% (SCRT)). Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Conclusion(s): In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher OP rate with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, should definitively answer this question.

Neoadjuvant endocrine therapy in postmenopausal women with HR+/HER2- breast cancer.

INTRODUCTION: While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women. AREAS COVERED: We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments. EXPERT OPINION: NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.

The Impact of Delay to Surgery on Oncological Outcomes for Colorectal Cancer Patients: A Global Prospective Cohort Study during the Sars-Cov- 2 Pandemic

Aim: The impact of a delay from treatment decision to surgery in colorectal cancer is unknown. The COVID-19 pandemic has provided a unique opportunity to ethically research the topic. This study aimed to compare the short-term oncological outcomes for colorectal cancer patients undergoing delayed versus non-delayed surgery. Method(s): This international prospective cohort study included consecutive colorectal cancer patients with a treatment decision for curative surgery, from February to July 2020. A delayed surgery was defined as being performed > 4 weeks after treatment decision. Further delays of 6 and 8 weeks after treatment decision were analysed. Surgical delays were analysed only in patients who did not receive neoadjuvant therapy. The primary outcome measure was poor oncological outcome, defined as progression to unresectable disease or positive resection margins. Result(s): Overall, 5453 patients from 47 countries were included, of which 9.6% (522/5453) did not receive the planned operation. Of the operated patients, 15.6% (767/4931) received neoadjuvant therapy. From the patients who went straight to surgery, 38.7% (1611/4164) were delayed beyond four weeks. Delayed patients were more likely to be older, male, more comorbid, have a higher BMI. Rectal cancers and early stage patients were more exposed to delay. After adjustment, delay was not associated with increased risk of a poor oncological outcome (OR = 0.89 (0.68-1.17, P = 0.415). Longer delays also did not show worse outcomes. Conclusion(s): One in ten colorectal cancer patients did not receive their planned operation during the COVID-19 pandemic. Delay to surgery did not impair short-term oncological outcomes and seems safe to be used during future pandemic waves if needed. Further research is needed to assess the long-term effects of surgical delay.

Pathology of neoadjuvant therapy and immunotherapy testing for breast cancer.

Neoadjuvant chemotherapy (NACT) has become the standard of care for high-risk breast cancer, including triple-negative (TNBC) and HER2-positive disease. As a result, handling and reporting of breast specimens post-NACT is part of routine practice, and it is important for pathologists to recognise the changes in tumour cells, tumour-associated stroma and background breast tissue induced by NACT. Familiarity with characteristic stromal features enables identification of the pre-treatment tumour site and allows confident diagnosis of pathological complete response (pCR) which is important for decisions concerning adjuvant therapy. Neoadjuvant endocrine therapy (NAET) is used less frequently than NACT; however, the SARS-COVID-19 pandemic has changed practice, with increased use as bridging therapy if surgery is delayed. NAET also induces characteristic changes in the tumour and stroma. Changes in the tumour microenvironment following NACT and NAET are also described. Immunotherapy is approved for use in advanced TNBC, and there are several trials exploring its role in early TNBC in the neoadjuvant setting. The current biomarker to determine eligibility for treatment with immune checkpoint inhibitors is programmed death ligand-1 (PD-L1) immunohistochemistry; however, this is complicated by lack of standardisation with different drugs linked to tests using different antibodies with different scoring systems. The situation in the neoadjuvant setting is further complicated by improved pCR rates for PD-L1-positive tumours in both immune therapy and placebo arms. Alternative biomarkers are urgently needed to identify which patients will derive benefit from immunotherapy and key candidates are discussed.

PET-derived parameters for response assessment in neoadjuvant atezolizumab: A secondary analysis of PRINCEPS phase II trial

Background: Immune Checkpoint Blockade (ICB) is moving from metastatic to curative setting in different diseases including NSCLC. While for metastatic disease radiological endpoints are currently the standard surrogate marker of benefit from ICBs, based on RECIST or PERCIST criteria, in neoadjuvant setting they often underestimate the response and then pathological response (PR) criteria were developed to evaluate Major PR (MPR), defined as ≤10% viable tumor cells after neoadjuvant treatment, and PR, defined as less than 50% residual tumor cells. Anyway, a non-invasive approach to determine the response to treatment is still an unmet need. Methods: PRINCEPS was a phase 2 clinical trial including limited-stage (IB-IIIA) NSCLC patients who received one administration of atezolizumab before surgery. 18-F FDG PET was performed within 28 days and after 15-22 days from atezolizumab. Surgery was performed at day 22-29 from atezolizumab. PET derived parameters including MTV and TLG was extracted by experienced nuclear physicians. Results: 30 patients were enrolled, all received A and underwent surgical resection after a median of 23 days. MPR was identified in 4, pPR in 8 tumors. Paired PET were available for 28 pts. Mean time from A to PET was 18 days (IQR 3.5). Total TLG and MTV reduction was not correlated with percentage of pPR (p=0.117 and p=0.843, respectively). Reduction of MTV (Pearson correlation 0.509, p=0.006) and TLG (Pearson correlation 0.562, p=0.002) in the primary tumor were strongly correlated with pPR, while no correlation was observed between percentage of pPR and variation in tumor diameters by RECIST criteria (-0.24, p=0.2) nor metabolic response (-0.12, p=0.55). The appearance of metabolically active hilar and mediastinal, non-pathological lymph nodes (LN) was noted in 12/28 patients, and specifically in. 2 out of 4 MPR and 5 out of 8 pPR. A trend toward an higher pPR was observed with LN appearance (mean 52% reduction in pts with LN appearance vs 29% without, p 0.061), probably reflecting immune activation. LN appearance was associated with hyperplasia and histiocytosis in resected, non-metastatic LNs. Conclusions: PET is able to early detect tumor response in localized NSCLC patients treated with ICBs in neoadjuvant setting. Clinical trial identification: NCT02994576. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Roche. Disclosure: N. Chaput-Gras: Financial Interests, Personal, Advisory Board, Strong-Iopredi Scientific Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Educational Session On Immune Cell Death: Servier;Financial Interests, Institutional, Expert Testimony, Expertise On Immune Cell Death Biomarkers: Servier;Financial Interests, Personal, Invited Speaker: Cytune Pharma;Financial Interests, Institutional, Research Grant, Research grant to identify immune biomarkers associated to clinical response in patients treated with agonistic mAbs: GSK;Financial Interests, Institutional, Research Grant, Preclinical studies in mice: GSK;Financial Interests, Institutional, Research Grant, Immune profiling of Head & Neck tumors: Sanofi. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Resea ch Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer-Ingelheim;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi;Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics;Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD;Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. 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. 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.

GALLANT-1: Galectin-3 (Gal-3) inhibitor GB1211 plus atezolizumab (atezo) in patients with non-small cell lung cancer (NSCLC)?A randomized, double-blind trial

Background: Gal-3 is a protein that binds specifically to N-acetylglucosamine-expressing carbohydrates, which are upregulated on key tumorigenic cell surface proteins. Gal-3 is widely over-expressed in the tumor microenvironment and is generally linked to poor outcomes. Gal-3 regulates immune cell function of T cells and macrophages, and promotes neovascularization and fibrosis [Peng Cancer Res 2008;Markowska J Biol Chem 2011;Kouo Cancer Immunol Res 2015]. Gal-3 sequesters interferon gamma, reduces T-cell influx, and contributes to tumor cell evasion of the immune system via LAG-3 activation [Chen PNAS 2009;Gordon-Alonso Nat Commun 2017]. Gal-3 has been identified as a marker of resistance to checkpoint inhibitors (CPIs);patients with stage IV NSCLC with high Gal-3 levels (> 70% Gal-3 immunohistochemical staining) have been shown to be resistant to the CPI pembrolizumab [Capalbo Int J Mol Sci 2019]. Animal data indicate synergy between CPI therapy and Gal-3 inhibition [Vuong Cancer Res 2019;Zhang FEBS Open Bio 2021]. Thus, inhibiting Gal-3 together with CPI-based immunotherapy may enhance tumor-specific immune responses, and overcome CPI resistance. Methods: GALLANT-1 (NCT05240131) is a 3-part, placebo-controlled phase Ib/IIa trial that will investigate safety and efficacy of GB1211 (a Gal-3 inhibitor) + atezo vs placebo + atezo in patients with advanced NSCLC. Part A will include 8-12 patients and study safety and tolerability of 200 mg and 400 mg GB1211 twice-daily + atezo (open-label). Primary endpoint is number of adverse events (AEs) after 12 weeks' treatment and will determine the dosage for Part B. Part B will include 75-94 patients, and is a randomized, double-blind study of GB1211 + atezo or placebo + atezo. Primary endpoints are safety (number of AEs) and efficacy (percentage change from baseline in the sum of longest diameter of target lesions after 12 weeks' treatment). Part C is an expansion study including patients from Parts A and B, with safety and efficacy assessments. Eligibility criteria: advanced or metastatic stage IIIB or IV NSCLC adenocarcinoma;measurable disease per RECIST v1.1;expression of programmed death ligand-1 on ≥50% of tumor cells;eligible for 1200 mg atezo every 3 weeks. Exclusion criteria: symptomatic, untreated, or actively progressing central nervous system metastases;prior systemic chemotherapy for treatment of recurrent advanced or metastatic disease, except if part of neoadjuvant/ adjuvant therapy;prior treatment with immune CPIs and/or GB1211;presence of EGFR mutation and ALK, ROS1, and RET alterations;treatment with antineoplastic or systemic immunotherapeutic agents prior to first GB1211 dose;severe infectious disease < 4 weeks prior to first GB1211 dose;active hepatitis B or C, HIV, or COVID-19. The study is being initiated;updated enrollment status will be presented at the meeting.

Preliminary outcomes for non-metastatic breast cancer before and during the coronavirus disease 2019 pandemic at community cancer centers

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has changed the delivery of cancer care and may have impacted the treatment outcomes. This study described the preliminary outcomes in non-metastatic breast cancer (BC) patients before and during the COVID-19 pandemic. Methods: This retrospective study included adult patients newly diagnosed with non-metastatic BC at two community cancer centers in southeast Texas. Patients diagnosed from 1/2018-10/2018 were included in the control group. Patients diagnosed from 4/2020-1/2021 were included in the COVID-19 group. The key outcomes were progression free survival (PFS), overall survival (OS), breast conserving surgery (BCS) rate, pathological complete response (PCR) rate, and time to treatment initiation (TTI). Results: The study included 74 patients (Table). The proportion of patients with self-detected BC was numerically higher in the COVID-19 group (55%) compared to the control group (36%), although this was not statistically significant (P = 0.09). The median follow-up periods were 38 (IQR: 36-43) months in the control group and 15 (IQR: 13-17) months in the COVID-19 group. No significant difference was observed in PFS (P = 0.74), with 1-year PFS of 93% (95%CI: 80%-98%) in the control group and 100% in the COVID-19 group. No significant difference was observed in OS (p = 0.22), with 1-year OS of 98% (95%CI 85%-100%) in the control group and 100% in the COVID-19 group. No significant difference was observed in TTI between control (51 days) and COVID-19 groups (52 days) (95%CI: -14 to 13;P = 0.91). Among patients who received neoadjuvant systemic therapy and surgery, BCS rates were 29% (5/17) in the control group and 50% (5/10) in the COVID-19 group (P = 0.42). Among patients who had triple negative or HER2 positive BC and received neoadjuvant systemic therapy and surgery, PCR rates were 57% (4/7) in the control group and 33% (1/3) in the COVID-19 group. Conclusions: Although total patient volume decreased during the COVID-19 pandemic, no significant difference was observed in clinical outcomes when comparing patients diagnosed with non-metastatic BC during and prior to the pandemic. Ongoing monitoring with a larger study population and longer followup period will help to elucidate the long-term impact of COVID-19 on BC treatment.