Final Analysis of the Phase 3 KEYNOTE-042 Study: Pembrolizumab (Pembro) Versus Platinum-Based Chemotherapy (Chemo) as First-Line Therapy for Patients (Pts) With PD-L1–Positive Locally Advanced/Metastatic NSCLC

Background

Pembro significantly improved OS vs chemo as first-line therapy in pts with PD-L1–positive locally advanced/metastatic NSCLC without EGFR/ALK alterations after median follow-up of 12.8 mo based on interim analysis of KEYNOTE-042 (NCT02220894). We present the final protocol-specified analysis with an additional 6 mo of follow-up.

Methods

Pts were randomized 1:1 to 35 cycles of pembro 200 mg Q3W or chemo (6 cycles of paclitaxel/pemetrexed [pem] + carboplatin with optional pem maintenance [nonsquamous only]), stratified by region (east Asia/non-east Asia), ECOG PS (0/1), histology (squamous/nonsquamous), and PD-L1 tumor proportion score (TPS; ≥50%/1%–49%). No α was allocated to OS in this analysis as the primary hypotheses for OS were met at the interim analysis. PFS differences (secondary endpoints) were assessed sequentially in pts with TPS ≥50%, ≥20%, and ≥1% using the stratified log-rank test (one-sided P = 0.01977, 0.02022, and 0.02065, respectively). Other secondary endpoints were ORR and safety. Duration of response (DOR) was an exploratory endpoint.

Results

1274 pts were randomized, 637 per arm. As of September 4, 2018 (median follow-up, 14 mo), 6% were receiving pembro and 3% were receiving pem maintenance. OS benefit with pembro vs chemo was maintained with longer follow-up (Table). PFS was not significantly improved with pembro vs chemo in pts with TPS ≥50%, therefore secondary efficacy hypotheses were not formally tested beyond TPS ≥50%. DOR was longer with pembro vs chemo (Table). Grade 3–5 treatment-related AEs were less frequent with pembro (18%) vs chemo (41%).

Conclusions

With an additional 6 mo follow-up, pembro demonstrated continued OS benefit vs chemo as first-line therapy in pts with locally advanced/metastatic PD-L1–positive NSCLC without EGFR/ALK alterations.

Clinical trial identification

NCT02220894.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by 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

T.S.K. Mok: Grants or research support: AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery; Speakers’ fees: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Taiho, Takeda Oncology; Honoraria: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd, Takeda Oncology, Janssen; Major stockholder: Sanomics Ltd.; Advisory board member: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd., Janssen, Takeda, ChiMed. Y-L. Wu: Honoraria: AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, Sanofi; Consulting, advisory role: AstraZeneca, Roche, Merck, Boehringer Ingelheim; Research funding to institution: Boehringer Ingelheim, Roche. B.C. Cho: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim; Consultant/advisor: AstraZeneca, Roche, Boehringer Ingelheim; Speakers’ bureau: AstraZeneca, BMS, Merck Sharp & Dohme, Novartis; Research funding: Bayer, AstraZeneca, Yuhan, Novartis. G. de Castro Jr: Consulting, advisory role: AstraZeneca, MSD, BMS, Roche, Novartis, Boehringer Ingelheim; Speakers’ bureau: MSD, BMS, Novartis, AstraZeneca; Travel, accommodation, expenses: MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca. K. Kubota: Research funding: Boehringer Ingelheim, Taiho, Ono; Speakers’ fees: Chugai, Taiho, MSD, Boehringer Ingelheim, AstraZeneca, BMS, Eli-Lilly, Daiichi Sankyo, Novartis, Ono, Dainippon-Sumitomo, Kyowa-Kirin, Eisai; Advisory role: Taiho. C. Caglevic: Consultant/advisor: BMS, MSD, Bayer, AZ; Speakers’ bureau: BMS, MSD, Bayer, Lilly, Roche; Research funding: MSD, Boehringer Ingelheim, GSK, Bayer, AZ, Medivation, Astellas Pharma, BMS; Travel, accommodation expenses: Boehringer Ingelheim, MSD. T. Dang, L. Yin, J. Penrod: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. G. Lopes: Research funding to institution: Merck & Co., Inc., EMD Serono, AstraZeneca. All other authors have declared no conflicts of interest.