Background

Superiority of 1L pembro monotherapy vs chemo in pts with metastatic NSCLC with PD-L1 TPS ≥50% and no sensitizing EGFR/ALK alterations was demonstrated in KEYNOTE-024 (NCT02142738). We report updated efficacy and safety from KEYNOTE-024 with 5 years follow-up.

Methods

Eligible pts were randomized to pembro (200 mg Q3W for up to 35 cycles [∼2 years]) or chemo. Randomization was stratified by ECOG PS (0/1), histology (squamous/nonsquamous), and region (East Asia/other). Pts randomized to chemo who had PD and met eligibility criteria could cross over to pembro monotherapy. Pts randomized to pembro who completed 2 years of therapy or who stopped pembro after achieving CR and then had PD were eligible for a second course of pembro monotherapy. Endpoints included PFS (primary); OS, ORR, and safety (secondary); and duration of response (exploratory). For this analysis, response/PD was assessed by investigators per RECIST v1.1.

Results

305 pts were randomized (pembro, 154; chemo, 151). As of June 1, 2020, median (range) time from randomization to data cutoff was 59.9 (55.1–68.4) mo. 83 (55.0%) pts randomized to chemo crossed over to pembro. Efficacy in the ITT population and in 39/154 (25.3%) pts in the pembro arm who completed 35 cycles of pembro are shown in the Table. 12/154 pts started second course pembro; outcomes in these pts will be presented. Among all treated pts, incidence of treatment-related grade 3–5 AEs was 31.2% with pembro vs 53.3% with chemo. Table: LBA51

Efficacy

Conclusions

Pembro continues to show improvements in OS vs chemo as 1L treatment for metastatic NSCLC with PD-L1 TPS ≥50%. Despite the high crossover rate, 5-year OS was approximately doubled among pts who received pembro (31.9% vs 16.3%). Fewer pts who received pembro experienced grade 3−5 AEs vs those who received chemo. Long-term OS and durable responses were observed with pembro monotherapy.

Clinical trial identification

NCT02142738.

Editorial acknowledgement

Medical writing assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA, USA). This assistance was funded by the study sponsor, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

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

J.R. Brahmer: Advisory/Consultancy: Merck. D. Rodriguez-Abreu: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer. A.G. Robinson: Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Pfizer . R. Hui: Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. N. Peled: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): NovellusDx; Honoraria (self), Research grant/Funding (self): Foundation Medicine; Honoraria (self), Research grant/Funding (self): Guardant360. S. Cuffe: Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Amgen. M. O'Brien: Advisory/Consultancy: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Roche. K. Hotta: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Honoraria (self): Ono; Honoraria (self): Kayaku; Honoraria (self): Taiho; Honoraria (self): Chugai. T.A. Leal: Advisory/Consultancy: Takeda; Advisory/Consultancy: Novocure; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech; Advisory/Consultancy: Inivata; Advisory/Consultancy: Merck; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: EMD Serono. J.W. Riess: Research grant/Funding (institution): Merck Sharp & Dohme Corp; Research grant/Funding (self): Spectrum; Research grant/Funding (institution): Revolution Medicines; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self): Blueprint Medicines; Honoraria (self): Medtronic; Advisory/Consultancy: Boehringer Ingelheim. E. Jensen: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. B. Zhao: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. M.C. Pietanza: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. M. Reck: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.