Effectiveness of PD-(L)1 inhibitors alone or in combination with platinum-doublet chemotherapy in first-line (1L) non-squamous non-small-cell lung cancer (Nsq-NSCLC) with PD-L1-high expression using real-world data.

Anti-programmed cell death protein (death-ligand) 1 [PD-(L)1] therapy alone [cancer immunotherapy (CIT)-mono] or combined with platinum-based chemotherapy (CIT-chemo) is used as the first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC). Our study compared clinical outcomes with CIT-mono versus CIT-chemo in the specific clinical scenario of non-squamous (Nsq)-NSCLC with a high PD-L1 expression of ≥50% [tumor proportion score (TPS) or tumor cells (TC)]. This was a retrospective cohort study using a real-world de-identified database. Patients with metastatic Nsq-NSCLC with high PD-L1 expression initiating first-line CIT-mono or CIT-chemo between 24 October 2016 and 28 February 2019 were followed up until 28 February 2020. We compared overall survival (OS) and real-world progression-free survival (rwPFS) using the Kaplan-Meier methodology. Hazard ratios (HRs) were adjusted (aHR) for differences in baseline key prognostic characteristics using the inverse probability of treatment weighting methodology. Patients with PD-L1-high Nsq-NSCLC treated with CIT-mono (n = 351) were older and less often presented with de novo stage IV disease than patients treated with CIT-chemo (n = 169). With a median follow-up of 19.9 months for CIT-chemo versus 23.5 months for CIT-mono, median OS and rwPFS did not differ between the two groups [median OS: CIT-chemo, 21.0 months versus CIT-mono, 22.1 months, aHR = 1.03, 95% confidence interval (CI) 0.77-1.39, P = 0.83; median rwPFS: CIT-chemo, 10.8 months versus CIT-mono, 11.5 months, aHR = 1.04, 95% CI 0.78-1.37, P = 0.81]. CIT-chemo showed significant and meaningful improvement in OS and rwPFS versus CIT-mono only in the never-smoker subgroup, albeit among a small sample of patients (n = 50; OS HR = 0.25, 95% CI 0.07-0.83, interaction P = 0.02; rwPFS HR = 0.40, 95% CI 0.17-0.95, interaction P = 0.04). Except in the subgroup of never-smoker patients, sparing the chemotherapy in first-line CIT treatment does not appear to impact survival outcomes in Nsq-NSCLC patients with high PD-L1 expression.

Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Disclosure MP reports grants, personal fees and non-financial support from Roche; grants, personal fees and non-financial support from AstraZeneca; personal fees and non-financial support from Merck Sharp and Dohme; grants, personal fees and non-financial support from Boehringer Ingelheim; grants, personal fees and non-financial support from Takeda; grants, personal fees and non-financial support from Chugai; personal fees from Novartis; personal fees from Amgen; personal fees and non-financial support from Pfizer; personal fees and non-financial support from Eli Lilly; personal fees and non-financial support from Bristol-Myers Squibb; personal fees from Illumina; personal fees from Daïchi Sankyo; and personal fees from Gritstone, outside the submitted work. EF reports personal fees from Abbvie, Amgen, AstraZeneca, Bayer, Blue Print Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Peervoice, Pfizer, prIME Oncology, Puma Biotechnology, Roche, Sanofi Genzyme, Springer, Takeda, Touchmedical, CME Outfitters, Beigene, Medical Trends, Peptomyc, Regeneron, Syneos Health and grants from Grant For Oncology Innovation (GOI), Fundación Merck Salud, outside the submitted work; Independent Member of the Board at Grífols. UD reports honorarium as Member of the Tumor Agnostic Evidence Generation working Group of Roche, outside the submitted work. LP reports to be an employee of Hoffmann-La Roche. NP reports to be a Genentech employee and hold Roche stocks. TGN Ton reports to be an employee of Hoffmann-La Roche and stock ownership of Hoffmann-La Roche. DM reports to be an employee of Hoffmann-La Roche and stock ownership of Hoffmann-La Roche. SM reports to be an employee of Hoffmann-La Roche. RS reports consultant or advisory role in the last two years for AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Regeneron, Roche, Seattle Genetics and Takeda; speaker honoria in the last two years from Amgen, AstraZeneca, Blueprint, Eli Lilly, GSK, MSD, Novartis, Roche and Sandoz; DMC in the last two years from Genentech/Roche and Takeda; financial support for ETOP and IBCSG trials (president and scientific chair) from AstraZeneca, Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pierre Fabre, Roche and Pfizer. SP reports personal fees from Amgen, Abbvie, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman – La Roche, Foundations Medicine, Illumina, Janssen, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Merck Sharp and Dohme, Merck Serono, Merrimack, Medscape, Phosphoplatin Therapeutics, Beigene, Imedex and grants from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffman – La Roche, Illumina, Novartis, Pfizer, Merck Sharp and Dohme, outside the submitted work. ZT has declared no conflicts of interest.