First-line pembrolizumab monotherapy in metastatic PD-L1 positive non-small cell lung cancer: A real-world analysis of time on treatment in US community oncology practices
Authors: V. Velcheti, S. Chandwani, X. Chen, M.C. Pietanza, T. Burke
Journal: Annals of Oncology (2018)

Background: Pembrolizumab monotherapy was approved for first-line (1L) treatment of metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% in October 2016 in the US, based on the findings from KEYNOTE-024 trial. A recent update of the trial with 25.2 months median follow-up demonstrated median pembrolizumab treatment duration of 7.9 months. The objective of our study is to estimate real-world time on treatment (rwToT) for 1L pembrolizumab monotherapy in a clinically matched real-world NSCLC database. Methods: This retrospective study utilized the Flatiron Health EHR-derived advanced NSCLC database from which patients with stage IV diagnosis, TPS ≥50%, at least one dose of 1L pembrolizumab monotherapy, and ECOG performance status (PS) 0-2 were included. Patients with missing or ECOG PS > 2 were excluded. rwToT was defined as the length of time between first and last administration date of pembrolizumab. Patients with a record of next line of therapy, or death, or whose last activity date was ≥120 days from the last administration date were considered discontinued; others were censored. The Kaplan-Meier (KM) estimates were generated for median rwToT, restricted mean (rMean) rwToT at maximum time point where at least 10% of patients have not discontinued, and landmark on-treatment rates. rMean rwToT at 24 months was also computed using the parametric function that provided best fit based on statistical testing and visual inspection criterion. All results were stratified into ECOG PS 0-1 (similar to KEYNOTE-024) and ECOG PS 2. Flatiron dataset from 31-Jul-2018 with median follow-up of 10.8 months was utilized. Results: Real-World Time on Treatment and On-Treatment Rate for First-Line Use of Pembrolizumab Monotherapy in Stage IV NSCLC, TPS ≥50%Table51OECOG 0-1ECOG 2N454172Mean age, years70.772.7N discontinued pembrolizumab (%)220 (48.5)114 (66.3)Median rwToT in months (95% CI)6.9 (5.7, 8.5)2.3 (1.4, 3.1)rMean rwToT in months (95% CI)6.9 (6.4, 7.4) [@12 months]3.7 (3.2, 4.3) [@9 months]Extrapolated rMean rwToT @ 24 months (95% CI)10.4 (9.3, 11.8) [Weibull]6.6 (4.8, 8.4) [Log Normal]6 months On-treatment rate in % (95% CI)54.1 (48.8, 59.1)32.0 (24.3, 39.9)12 months On-treatment rate in % (95% CI)36.8 (31.0, 42.6)-/-18 months On-treatment rate in % (95% CI)31.7 (25.2, 38.4)-/- Open table in a new tab Conclusions: In the real-world, duration of pembrolizumab use for 1L metastatic NSCLC is similar to KEYNOTE-024 when restricted to a trial-matched population of ECOG 0-1 patients. Duration of use tended to be however shorter in a real-world population of ECOG 2 patients who are commonly excluded from clinical trials. Legal entity responsible for the study: Funding and support for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure: V. Velcheti: Advisory/consultant role: Merck, Bristol-Myers Squibb, AstraZeneca, Genentech, Celgene, Takeda, Foundation Medicine, Nektar Therapeutics. S. Chandwani, X. Chen, M.C. Pietanza, T. Burke: Employee and shareholder: Merck & Co., Inc., Kenilworth, NJ, USA.