Original Article
Non–Small Cell Lung Cancer
A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407

Results from this study were presented, in part, at the 2019 European Society for Medical Oncology Congress in Barcelona, Spain, September 29, 2019.
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Abstract

Introduction

In the randomized KEYNOTE-407 study (ClinicalTrials.gov, NCT02775435), pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (chemotherapy) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC. We report updated efficacy outcomes from the protocol-specified final analysis and, for the first time, progression on next line of treatment.

Methods

Eligible patients were randomized to chemotherapy plus either pembrolizumab (n = 278) or placebo (n = 281). After positive results from the second interim analysis, patients still receiving placebo could cross over to pembrolizumab monotherapy at the time of confirmed progressive disease. The primary end points were OS and PFS. PFS-2 (time from randomization to progression on next-line treatment/death, whichever occurred first) was an exploratory end point.

Results

After median (range) follow-up of 14.3 (0.1–31.3) months, pembrolizumab plus chemotherapy continued to exhibit a clinically meaningful improvement over placebo plus chemotherapy in OS (median, 17.1 mo [95% confidence interval (CI): 14.4‒19.9] versus 11.6 mo [95% CI: 10.1‒13.7]; hazard ratio [HR], 0.71 [95% CI: 0.58‒0.88]) and PFS (median, 8.0 mo [95% CI: 6.3‒8.4] versus 5.1 mo [95% CI: 4.3‒6.0]; HR, 0.57 [95% CI: 0.47‒0.69]). PFS-2 was longer for patients randomized to first-line pembrolizumab plus chemotherapy (HR, 0.59 [95% CI: 0.49‒0.72]). Grade 3 to 5 adverse events occurred in 74.1% and 69.6% of patients receiving pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively.

Conclusions

Pembrolizumab plus chemotherapy continued to exhibit substantially improved OS and PFS in patients with metastatic squamous NSCLC. The PFS-2 outcomes support pembrolizumab plus chemotherapy as a standard first-line treatment in patients with metastatic squamous NSCLC.

Keywords

PD-L1
Pembrolizumab
Chemotherapy
Squamous non–small-cell lung cancer

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Disclosure: Dr. Paz-Ares reports receiving honoraria (self/spouse) for scientific advice or as a speaker for Adacap, Amgen, AstraZeneca, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Eli Lilly, Merck Sharp & Dohme, Merck, Novartis, PharmaMar, Pfizer, Roche, Sanofi, Servier, and Sysmex; is a board member for Genómica and Altum Sequencing; and has received grants for the institution from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Pfizer. Dr. Vicente reports receiving honoraria (self/spouse) for scientific advice or as a speaker from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche. Dr. Robinson reports receiving funding for clinical trials from AstraZeneca, Merck, Pfizer, and Roche; and is an advisory board member for Merck. Dr. Soto Parra is an advisory board member for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, and Roche. Dr. Mazières reports receiving honoraria from AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, Merck, Merck Sharp & Dohme, Pfizer, PharmaMar, Pierre Fabre, and Roche; and grants for the institution from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche. Dr. Hermes reports receiving travel accommodations from Eli Lilly and PharmaMar; honoraria for lectures or scientific advice from Bristol-Myers Squibb and Pfizer; and funding for the institution from Bayer, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, PharmaMar, and Roche. Dr. Cicin is an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme, and Pfizer; has received personal fees for lectures from Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Quintiles, and Roche; and funding for the institution to support trial conduct from Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Parexel, Pfizer, Quintiles, and Taiho. Dr. Medgyasszay reports receiving honoraria for lectures from Merck, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, and Novartis; and funding on behalf of the institution to support trial conduct from Merck, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, Novartis, Astellas, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Parexel, Pfizer, Quintiles, and Taiho. Dr. Rodríguez-Cid reports receiving funding on behalf of the institution during the conduct of this trial from Merck Sharp & Dohme, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis, and Roche. Dr. Okamoto reports receiving grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Merck Sharp & Dohme Oncology, Ono Pharmaceutical, and Taiho; personal fees from Pfizer; and grants from AbbVie, Astellas Pharma, and Novartis. Dr. Ramlau reports receiving honoraria (self/spouse) as a scientific adviser or as a speaker from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Sanofi; and is a board member for AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Drs. Deng, Zhang, and Bas are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Piperdi is an employee of and owns stock in Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Dr. Halmos reports receiving research funding from AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Guardant Health, Merck, Mirati, Novartis, Pfizer, and Takeda; and is a consultant for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Guardant Health, Merck, Novartis, Pfizer, and Spectrum. Drs. Tafreshi, Lee, Vladimirov, and Cheng report receiving funding on behalf of their institutions from Merck to support study conduct.