ABSTRACT
Background: In the Phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in PFS and OS (OS HR 0.77;95% CI 0.65-0.92;p=0.0030;mFU 34.9 mo in censored pts) vs CT alone in pts with mNSCLC. D+CT showed a statistically significant improvement in PFS and a positive trend for OS improvement vs CT that did not reach significance (OS HR 0.86;95% CI 0.72-1.02;p=0.0758). Here we report an updated exploratory analysis of OS, and histology and mutational status subgroups, after a mFU of ~4 y. Method(s): Pts with EGFR/ALK wild-type mNSCLC were randomised 1:1:1 to 1L D (until progression) +/- limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles);or CT (up to 6 cycles). Alpha-controlled endpoints were PFS and OS for D+CT vs CT and T+D+CT vs CT. Pt tumours were molecularly characterised via sequencing of tissue and/or ctDNA samples. Result(s): At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75;95% CI 0.63-0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84;95% CI 0.71-0.99;3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous;data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU. [Formula presented] Conclusion(s): The results of this exploratory analysis from POSEIDON, after mFU of ~4 y, demonstrate the durable long-term OS benefit of adding a limited course of T to D and 4 cycles of CT. These data support the use of this regimen as a 1L treatment option for pts with mNSCLC, including harder-to-treat mutational subgroups such as STK11m, KEAP1m or KRASm. Clinical trial identification: NCT03164616 (release date: 23 May 2017). Editorial acknowledgement: Medical writing support for the development of this , under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca PLC. Funding(s): AstraZeneca. Disclosure: B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc;Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp., J INTS BIO;Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp, J INTS BIO;Financial Interests, Personal, Royalties: Champions Oncology;Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp;Financial Interests, Personal, Advisory Role, Consulting: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines;Financial Interests, Personal, Other: DAAN Biotherapeutics. J.A. Alatorre Alexander: Financial Interests, Personal, Speaker's Bureau: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen;Financial Interests, Personal, Advisory Board: BMS, Roche, AstraZeneca, MSD, Boehringer Ingelheim, Takeda, Eli Lilly, Janssen. S. Lucien Geater: Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Novartis, Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer. K. Sang-We: Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial I terests, Personal, Research Grant: Yuhan;Non-Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Boehringer Ingelheim, Norvatis, Lilly, Takeda, Therapex, and Yuhan. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie, Aptitude Health, AstraZeneca, Biopahrama, BMS, Exelixis, Mirati Therapeutics, Cardinal Health, Coherus Biosciences, Athenex, Karyopharm Therapeutics, IntegraConnect, Oncocyte. C.T. Yang: Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Merck, Amgen, Johnson & Johnson, AbbVie, Hanso Pharma, Roche, Ono, BMS, Chugai. L.H. Araujo: Financial Interests, Personal, Invited Speaker: MSD, Roche, Pfizer, AstraZeneca, Takeda, Lillly, Janssen, Amgen, Novartis, BMS, Sanofi;Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, AstraZeneca, Sanofi. H. Saito: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, ONO Pharmaceutical;Financial Interests, Personal, Principal Investigator: AstraZeneca, Chugai Pharmaceutical ONO Pharmaceutical, Bristol Myers Squibb. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, Janssen, Lilly, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Hoffmann-La Roche, Janssen, MSD, Merck, Pfizer, and Takeda;Financial Interests, Personal, Other: Symphogen: Data Safety Monitoring Board. Z. Lai, H. Mann, X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure;Financial Interests, Institutional, In ited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati;Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier;Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca;Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS;Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS;Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK;Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD;Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati;Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar;Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics;Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01;chair ALEX;steering committee BFAST;steering committee BEAT-Meso;steering committee ImPower-030, IMforte: Roche/Genentech;Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos;Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO;Non-Financial Interests, Personal, Officer, Council Me ber & Scientific Committee Chair: ETOP/IBCSG Partners;Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities;Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Bejart Lausanne Foundation;Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK;Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR;Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO;Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK;Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO;Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. E.B. Garon: Financial Interests, Personal, Advisory Board: ABL Bio, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, Eisai, Eli Lilly, EMD Serono, Gilead, GSK, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio Therapeutics;Financial Interests, Personal, Research Grant: ABL Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, EMD Serono, Genentech, Iovance Biotherapeutics, Eli Lilly, Merck, Mirati Therapeutics, Neon Therapeutics, Novartis. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, BI, BMS, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Limi, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians' Education Resource, Pfizer, PrIME Oncology, Research to Practice, RochePharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., T;Financial Interests, Personal, Advisory Board: AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim Pharmaceuticals Inc., Bristol Myers Squibb Company, C4 Therapeutics, Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lily, Loxo-Oncology Inc., Lunit, Inc., Mer k Serono, Merck Sharp & Dohme, Mirati Therapeutics, Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnolo;Financial Interests, Personal, Member of the Board of Directors: AstraZeneca PLC, HutchMed;Financial Interests, Personal, Full or part-time Employment: The Chinese University of Hong Kong (Full-Time);Financial Interests, Personal, Stocks/Shares: Aurora Tele-Oncology Ltd., HutchMed, Act Genomics-Sanomics Group, Loxo-oncology, Virtus Medical Group and Lunit USA, Inc;Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery;Financial Interests, Personal, Leadership Role: Lunit USA, Inc., ACT Genomics-Sanomics Group, Aurora;Financial Interests, Personal, Other, Independent contractor: AbbVie Inc., ACEA Pharma, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., Ltd., AstraZeneca (before 1/1/19), BeiGene, Berry Oncology, BI, Blueprint Medicines Corporation, BMS, C4 Therapeutics, Inc, CStone Pharmaceuticals, Curio Science, Daiichi Sa, Loxo-Oncology, Merck Serono, MSD, Mirati Therapeutics Inc., MoreHealth, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Roche Pharmaceuticals, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Takeda Pharmaceuticals HK Ltd., Vert, Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/ WebMD, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHea. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie;Acerta;Adaptimmune;Amgen;Apexigen;Arcus B osciences;Array BioPharma;Artios Pharma;AstraZeneca;Atreca, BeiGene;BerGenBio;BioAtla;Boehringer Ingelheim, Calithera Biosciences;Checkpoint Therapeutics;Corvus Pharmaceuticals;Curis;CytomX, Daiichi Sanyo;Dracen Pharmaceuticals;Dynavax, Eli Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan Kettering, Merck, Merus, Mirati Therapeutics, NeoImmuneTech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics;Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, IDEAYA Biosciences, iTeos, Janssen, Merck, Mirati Therapeutics, Novartis, Oncorus, Regeneron Pharmaceuticals, Revolution Medicines, Ribon Therapeutics, Sanofi, Turning Point Therapeutics, WindMIL. All other authors have declared no conflicts of interest. Copyright © 2022
ABSTRACT
Introduction: Previously reported data on patients with thoracic malignancies who develop COVID-19 have suggested a higher mortality rate compared to the general population and to other cancer types, particularly in patients over 65 years of age or suffering from active or progressive disease. Preliminary data from other studies have suggested that gender and ethnicity may also impact patient outcomes. Methods: TERAVOLT is a multi-center, international observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria include the presence of any thoracic cancer and a COVID-19 diagnosis confirmed in the laboratory with RT-PCR/serology, highly suspicious radiological and clinical findings, or suspected with symptoms and known contact with a positive person. The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Clinical outcomes including hospitalization, ICU admission, oxygen requirement and mortality were collected. The association between demographic/clinical characteristics and outcomes were measured with odds ratio with 95% confidence intervals using a logistic regression model. Results: As of August 20, 2020, a total of 1,053 patients with COVID-19 and thoracic cancers from 19 countries and 130 centers have been identified, including 42% females and 84% White, 9.3% African American, 25% Hispanic. The median age of male patients was 69 compared to 66 years of age for females. While ECOG PS was similar between treatment groups, 77% of males were admitted to hospital with a mortality rate of 37% compared to 66% of females with a mortality rate of 28%. The median age of African American patients was 66 years of age compared to 68 and 69 years of age for white and Hispanic patients, respectively;26% of African American and 25% White patients had an ECOG PS ≥2 compared to 19% of Hispanics. A similar percentage of patients were admitted to the hospital and ICU, while the mortality rate for Hispanics was 36% compared to 34% for whites and 26% for African Americans. Conclusion: Similar to the general population, the mortality rate of males with thoracic cancer is higher than females. Regarding ethnicity, there is a difference in the median age of African American patients compared to Whites and Hispanics. Although the severity of COVID-19 disease, as defined by hospital admission, is similar between ethnic groups, the mortality rate in Hispanics is higher. We will present a multivariate analysis of these data according to gender and ethnicity, including the impact of cancer stage, prior cancer therapy, and COVID-19 therapy on outcomes. Keywords: TERAVOLT, international COVID-19 registry, thoracic malignancies