LBA11 - IPSOS: Results from a phase III study of first-line (1L) atezolizumab (atezo) vs single-agent chemotherapy (chemo) in patients (pts) with NSCLC not eligible for a platinum-containing regimen

Background

In IMpower110 (NCT02409342), 1L atezo (anti–PD-L1) improved OS vs platinum-doublet chemo (PDC) in pts with PD-L1–high NSCLC and ECOG PS ≤1. However, ≥40% of NSCLC pts have poor ECOG PS (≥2) and/or substantial comorbidities, resulting in ineligibility for platinum-based chemo and most 1L clinical trials. IPSOS is a global, multicenter, open-label, randomised Phase 3 study of atezo vs single-agent chemo in pts ineligible for 1L PDC.

Methods

Pts had locally advanced/metastatic NSCLC without driver mutations and were ineligible for 1L PDC due to poor PS (≥2) or comorbidities in pts aged ≥70 yr. Pts were randomised 2:1 to atezo 1200 mg IV every 3 wk or single-agent chemo (vinorelbine or gemcitabine) in 3- or 4-wk cycles. The primary endpoint was OS. Key secondary endpoints were OS rates, ORR, PFS, DOR and OS and PFS in PD-L1+ pts. Safety and health-related quality of life were also assessed.

Results

453 pts were randomised (302 atezo; 151 chemo). Median age was 75 yr (range, 33-94), 31% were ≥80 yr, 72% were male and 83% had ECOG PS ≥2. At data cutoff (30 Apr 2022), with a median follow-up of 41.0 mo, atezo significantly improved OS vs chemo (stratified HR, 0.78; 95% CI: 0.63, 0.97; P=0.028), with a consistent benefit seen across key subgroups, including PD-L1 expression levels, PS and histology. Benefit was seen in 2-yr OS rate, ORR and DOR (Table). Gr 3/4 TRAEs occurred in 16.3% and 33.3% of pts and Gr 5 TRAEs in 1.0% and 2.7% of pts in the atezo and chemo arms, respectively. Atezo improved TTCD of chest pain vs chemo (HR, 0.51; 95% CI: 0.27, 0.97); meaningful improvements from baseline were also seen for appetite loss and cough.

Conclusions

1L atezo improved OS vs chemo in platinum-ineligible pts with NSCLC, with twice as many pts estimated to be alive at 2 yr when treated with atezo vs chemo. No new or unexpected safety concerns were seen in this poor prognosis population. Table: 000LBA11

^aStratified.

Clinical trial identification

NCT03191786.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Marcia Gamboa, PhD of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

C. Schulz: Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal and Institutional, Principal Investigator: Roche; Financial Interests, Personal, Advisory Role: Roche. K. Prabhash: Financial Interests, Institutional, Advisory Board, Novartis, Merick; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Alkem. D.L. Cortinovis: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: MSD, BMS, Novartis, Boehringer Ingelheim, Amgen, Roche, Sanofi Genzyme, Takeda. A. Rittmeyer: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer-Ingelheim, Eli Lilly, GSK, Novartis, MSD, Pfizer, Roche Genentech. D. Vicente Baz: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Roche, MSD, Bayer, Pfizer, Sanofi; Financial Interests, Personal, Consultancy: AstraZeneca, Roche, MSD, Bayer, Pfizer; Financial Interests, Personal, AstraZeneca; Financial Interests, Personal, Travel, Accommodations: AstraZeneca, MSD, Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Speaker Honoraria: Takeda, Bristol Myers Squibb. R. Califano: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, Bayer, Janssen and Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly Oncology, Roche, Pfizer, MSD, Takeda, Amgen, Janssen; Financial Interests, Personal, Speaker in educational activities: Medscape and Peervoice; Financial Interests, Personal, Ownership Interest, Partnership: The Christie Private Care - LOC; Financial Interests, Institutional, Invited Speaker, Principal Investigator for clinical trial: Roche, AstraZeneca, Pfizer, Clovis, Lilly Oncology, MSD, BMS, AbbVie, Takeda, Jannsen, and Novartis; Non-Financial Interests, Member of Lung Group: EORTC. G. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Takeda, Jazz, EMD Serono, Pfizer, Merck, Novartis, Amgen; Financial Interests, Institutional, Sponsor/Funding: Takeda, Boehringer-Ingelheim; Financial Interests, Personal, Sponsor/Funding: Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MSD. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, MSD, Roche. Y. Hu: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Morris: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. E.K. Hoeglander: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. M. Connors: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. H.K.M. Vollan: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. 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, Invited 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, 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: PharmaMar; 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, Officer, LEadeship Role: ESMO President 2020-2022: ESMO; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Involved in Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR; Non-Financial Interests, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Member, Association of Swiss interns and residents: ASMAC/VSAO. All other authors have declared no conflicts of interest.