5MO - Patient-reported outcomes (PROs) with 1L durvalumab (D), with or without tremelimumab (T), plus chemotherapy (CT) in metastatic (m) NSCLC: Results from POSEIDON

Background

In the phase 3 POSEIDON study, 1L D + CT significantly improved PFS vs CT alone in pts with mNSCLC, with a positive trend for OS improvement that did not reach statistical significance. 1L T + D + CT demonstrated statistically significant and clinically meaningful improvements in both PFS and OS vs CT. Here we describe analyses of PROs for T + D + CT and D + CT vs CT alone.

Methods

Pts (n=1013) with EGFR/ALK wild-type mNSCLC were randomised (1:1:1) to 1L T 75 mg + D 1500 mg + platinum-based CT q3w for ≤4 cycles, followed by D q4w until progression, with one additional dose of T post-CT (wk 16); D + CT q3w for ≤4 cycles, followed by D q4w until progression; or CT q3w for ≤6 cycles. Global health status/QoL, functioning and symptoms were assessed as a secondary endpoint using EORTC QLQ-C30/LC13. Time to deterioration (TTD) was assessed using a stratified log-rank test with a Cox proportional-hazards model, with medians estimated by the Kaplan-Meier method, and improvement rates by logistic regression.

Results

As of 12 March 2021, 338, 338 and 337 pts were randomised to T + D + CT, D + CT and CT, respectively. Compliance was ≥60% for C30 and LC13 up to 88 wks, 64 wks and 24 wks for the T + D + CT, D + CT and CT arms, respectively. Baseline global health status/QoL, functioning and symptom scores were generally similar across treatment arms. HRs indicated longer TTD with T + D + CT and D + CT vs CT across nearly all PROs, including prespecified symptoms/domains of interest (with exception of appetite loss [C30] for D + CT vs CT; Table). Improvement rates in PROs, including prespecified symptoms/domains of interest, were greater for T + D + CT and D + CT vs CT alone; details will be presented.Table: 5MO

TTD for prespecified symptoms/domains of interest

Conclusions

The addition of D (+/- T) to CT improved efficacy while delaying deterioration in health-related QoL in pts with mNSCLC. Pts in the T + D + CT and D + CT arms tended to have longer TTD and greater rates of improvement in global health status/QoL, functioning and symptoms vs pts in the CT arm.

Clinical trial identification

NCT03164616 (release date: May 23, 2017).

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by James Holland, PhD, of Ashfield MedComms (Macclesfield, UK), an Ashfield Health company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

E.B. Garon: Financial Interests, Personal, Advisory Board: ABL Bio; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Dracen Pharmaceuticals; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Personalis; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Shionogi; Financial Interests, Personal, Advisory Board: Xilio Therapeutics; Financial Interests, Institutional, Research Grant: ABL Bio; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Dynavax Technologies; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Neon Therapeutics; Financial Interests, Institutional, Research Grant: Novartis. B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc; Financial Interests, Personal, Advisory Board: Brigebio therapeutics; Financial Interests, Personal, Advisory Board: Cyrus therapeutics; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Joseah BIO; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: MOGAM Institute; Financial Interests, Personal, Research Grant: Dong-A ST; Financial Interests, Personal, Research Grant: Champions Oncology; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Yuhan; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Dizal Pharma; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Medpacto; Financial Interests, Personal, Research Grant: GIInnovation; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Blueprint medicines; Financial Interests, Personal, Research Grant: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc; Financial Interests, Personal, Stocks/Shares: Gencurix Inc; Financial Interests, Personal, Stocks/Shares: Bridgebio therapeutics; Financial Interests, Personal, Stocks/Shares: KANAPH Therapeutic Inc; Financial Interests, Personal, Stocks/Shares: Cyrus therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role, Consulting role: Novartis; Financial Interests, Personal, Advisory Role, Consulting role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role, Consulting role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting role: Ono; Financial Interests, Personal, Advisory Role, Consulting role: Yuhan; Financial Interests, Personal, Advisory Role, Consulting role: Pfizer; Financial Interests, Personal, Advisory Role, Consulting role: Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting role: Janssen; Financial Interests, Personal, Advisory Role, Consulting role: Takeda; Financial Interests, Personal, Advisory Role, Consulting role: MSD; Financial Interests, Personal, Advisory Role, Consulting role: Janssen; Financial Interests, Personal, Advisory Role, Consulting role: Medpacto; Financial Interests, Personal, Advisory Role, Consulting role: Blueprint medicines; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. J. Alatorre-Alexander: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Advisory Board: Janssen. S. Kim: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Personal, Funding: Yuhan; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Yuhan. M. Hussein: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Cardinal Health; Financial Interests, Personal, Advisory Board: Coherus Bioscience; Financial Interests, Personal, Advisory Board: Athenex; Financial Interests, Personal, Advisory Board: Kyopharm; Financial Interests, Personal, Advisory Board: Integra. H. Saito: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Personal, Principal Investigator: Ono Pharmaceutical. N. Reinmuth: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Boehringer-Ingelheim; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Hoffmann-La Roche; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Takeda. N. Medic: Financial Interests, Personal, Full or part-time Employment, Full time employee: AstraZeneca. H. Mann: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. X. Shi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, Oncology Education, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda, Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, GSK, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics, Roche/Genentech. T.S.K. Mok: Financial Interests, Personal, Advisory Role: AbbVie, Inc.; Financial Interests, Personal, Advisory Role: ACEA Pharma; Financial Interests, Personal, Advisory Role: Alpha Biopharma Co. Ltd.; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Amoy Diagnostics Co. Ltd.; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Blueprint Medicines Corporation; Financial Interests, Personal, Advisory Role: CStone Pharmaceuticals; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Fishawack Facilitate Ltd.; Non-Financial Interests, Personal, Advisory Role: geneDecode; Financial Interests, Personal, Advisory Role: Gritstone Oncology Inc.; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Hengrui Therapeutics; Financial Interests, Personal, Advisory Role: Ignyta Inc.; Financial Interests, Personal, Advisory Role: IQVIA; Financial Interests, Personal, Advisory Role: Incyte Corporation; Financial Interests, Personal, Invited Speaker: InMed Medical Communication; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Loxo-Oncology; Financial Interests, Personal, Other, consulting, advisory, lectures, Board of Director (NEID) from Mar 2021 onwards; stock options: Lunit USA, Inc.; Financial Interests, Personal, Invited Speaker: MD Health (Brazil); Financial Interests, Personal, Other, Lectures: Medscape/WebMD; Financial Interests, Personal, Other, Lectures: Merck Serono; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Mirati Therapeutics Inc.; Financial Interests, Personal, Advisory Role: MoreHealth; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: OrigiMed; Financial Interests, Personal, Invited Speaker: PeerVoice; Financial Interests, Personal, Invited Speaker: Physicians' Education Resource; Financial Interests, Personal, Invited Speaker: P. Permanyer SL; Financial Interests, Personal, Advisory Role, consulting, advisory, lectures: Pfizer, Inc; Financial Interests, Personal, Invited Speaker: PrIME Oncology; Financial Interests, Personal, Advisory Role: Puma Biotechnology Inc; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Advisory Role, consulting, advisory, lectures: Roche; Financial Interests, Personal, Advisory Role, consulting, advisory, lectures: Sanofi-Aventis R&D; Financial Interests, Personal, Advisory Role, consulting, advisory, lectures: Takeda; Financial Interests, Personal, Invited Speaker: Touch Medical Media; Financial Interests, Personal, Advisory Role: Virtus Medical Group; Financial Interests, Personal, Advisory Role: Yuhan Corporation; Financial Interests, Personal, Member of the Board of Directors, Board of Director (NED) from Jan 2019 onwards: AstraZeneca PLC; Financial Interests, Personal, Member of the Board of Directors, Board of Director (INED) from Oct 2018 onwards; Shareholder; advisory: HutchMed; Financial Interests, Personal, Member of the Board of Directors, Board of Director (Board Chairman); from 2015 onwards; Shareholder: Act Genomics-Sanomics Group; Financial Interests, Personal, Other: Clovis Oncology; Financial Interests, Personal, Advisory Role: SFJ Pharmaceuticals; Financial Interests, Personal, Other: XCovery; Financial Interests, Personal, Advisory Role: Curio Science; Financial Interests, Personal, Advisory Board: Inivata; Financial Interests, Personal, Advisory Board: Berry Oncology; Financial Interests, Personal, Advisory Board: G1 Therapeutics Inc.; Financial Interests, Personal, Member of the Board of Directors, Board of Director from Sep 2020; consulting; Shareholder: Aurora; Financial Interests, Personal, Advisory Role: Qiming Development (HK) Ltd.; Financial Interests, Personal, Invited Speaker: Daz Group; Financial Interests, Personal, Invited Speaker: Lucence Health Inc.; Financial Interests, Personal, Invited Speaker: Merck Pharmaceuticals HK Ltd; Financial Interests, Personal, Invited Speaker: Shanghai BeBirds Translation & Consulting Co., Ltd; Financial Interests, Personal, Invited Speaker: Liangyihui Network Technology Co., Ltd; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Advisory Role: Gilead Sciences, Inc; Financial Interests, Personal, Advisory Role: Vertex Pharmaceuticals; Financial Interests, Personal, Advisory Role: Covidien LP; Financial Interests, Personal, Advisory Role: Elevation Oncology; Financial Interests, Personal, Advisory Role: C4 Therapeutics, Inc. M. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo; Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera, CytomX, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, GlaxoSmithKlein, Grit. All other authors have declared no conflicts of interest.