Recent data suggest that the overall survival (OS) and progression-free survival (PFS) observed in RW patients with mNSCLC receiving IO regimens may be shorter than that seen in randomised clinical trials (RCTs). This retrospective, observational study describes rwOS and rwPFS (overall and by PD-L1 expression) compared with the outcomes observed in RCTs in patients with mNSCLC.
Eligible RW patients from the US Flatiron Enhanced Data-Mart database were those who developed stage IV mNSCLC, initiated 1L treatment with IO ± CT between 1 Nov 2016 and 31 May 2021, and met select eligibility criteria of 6 RCTs for IO regimens with a US approval in mNSCLC: KEYNOTE (KN) -024, KN-189, KN-407, IMpower150, CheckMate (CM) 9LA, and CM 227. Patients with brain metastases at diagnosis were excluded. Efficacy-effectiveness factors (EEFs) allowed evaluation of the gaps between RW and RCT outcomes.
Most patient baseline characteristics (e.g., % male, ECOG/WHO performance status [PS], PD-L1 expression, and smoking status) differed by <10% between the RW and RCT datasets. Among patients with ECOG PS 0–1, rwOS and rwPFS were considerably shorter vs RCTs, with EEF ratios between 42–73% and 53–78%, respectively (Table). Similar results were observed by PD-L1 status, as applicable (not shown). Where sample size allowed, expanding the analysis to cohorts of PS 2 and PS 3–4, separately, showed even greater disparities in outcomes (not shown). EEF: estimated as median from RW/median from RCT ×100 m, median (months); NE, not estimable.
RCT Dataset mOS 95% CI OS EEF, % mPFS 95% CI PFS EEF, % KN-024 pembro RCT 154 30.0 18.3–NE 54.0 10.3 6.7–NE 56.3 RW 796 16.2 13.9–18.7 5.8 4.9–6.7 KN-189 pembro+CT RCT 410 22.0 19.5–25.2 55.9 9.0 8.1–9.9 65.6 RW 1836 12.3 11.3–13.3 5.9 5.6–6.2 KN-407 pembro+CT RCT 278 17.2 14.4–19.7 72.7 8.0 6.3–8.5 77.5 RW 412 12.5 10.1–14.9 6.2 5.4–7.3 IMpower150 atezo+bev+CT RCT 19.5 17.0–22.2 60.0 8.3 7.7–9.8 67.4 RW 31 11.7 8.1–27.2 5.6 3.6–9.8 CM 9LA nivo+ipi+CT RCT 15.8 13.9–19.7 69.0 6.4 5.5–7.8 53.1 RW 17 10.9 2.0–NE 3.4 1.2–5.9 CM 227 nivo+ipi RCT 17.1 15.0–20.2 42.1 5.1 4.1–6.3 76.5 RW 35 7.2 3.0–NE 3.9 1.4–6.9
IO has been established as the standard of care in mNSCLC; however, RW survival outcomes are considerably shorter than those reported in pivotal RCTs, even for indicated populations in the RW. Despite some limitations of the dataset and the US-only population, our RW findings are broadly consistent with other RW studies, highlighting the unmet need for more effective treatment options for RW patients with mNSCLC.
Medical writing support for this abstract, under the direction of the authors, was provided by Gauri Saal, MA Economics, of INIZIO Medical, and was funded by AstraZeneca.
AstraZeneca.
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, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, 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 Member & 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 Béjart 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), ASCO, AACR, IASLC; 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. R.J. Salomonsen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. R. Tattersfield: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Wang: Financial Interests, Personal, Full or part-time Employment, Contractor (PHASTAR): AstraZeneca. Y. Xiao: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. L. Cai: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Sadow: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. R. Jassim: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S.V. Liu: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Lilly, Merck/MSD, Novartis, Regeneron, Sanofi, Takeda, Turning Point Therapeutics; Financial Interests, Personal, Principal Investigator: Alkermes, Blueprint, Bristol-Myers Squibb, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, Pfizer, RAPT, Turning Point Therapeutics; Financial Interests, Personal, Invited Speaker: Merck, Genentech, AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck, Genentech, AstraZeneca.