Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer

KEYNOTE-407 Investigators

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. METHODS: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival. RESULTS: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%). CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

Original languageEnglish (US)
Pages (from-to)2040-2051
Number of pages12
JournalThe New England journal of medicine
Volume379
Issue number21
DOIs
StatePublished - Nov 22 2018

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Non-Small Cell Lung Carcinoma
Drug Therapy
Confidence Intervals
Placebos
Survival
Disease-Free Survival
Carboplatin
Paclitaxel
Nanoparticles
Ligands
pembrolizumab
Platinum
Disease Progression
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. / KEYNOTE-407 Investigators.

In: The New England journal of medicine, Vol. 379, No. 21, 22.11.2018, p. 2040-2051.

Research output: Contribution to journalArticle

KEYNOTE-407 Investigators. / Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. In: The New England journal of medicine. 2018 ; Vol. 379, No. 21. pp. 2040-2051.
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title = "Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer",
abstract = "BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50{\%} of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. METHODS: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival. RESULTS: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95{\%} confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95{\%} CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95{\%} CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95{\%} CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95{\%} CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95{\%} CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8{\%} of the patients in the pembrolizumab-combination group and in 68.2{\%} of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3{\%} vs. 6.4{\%}). CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).",
author = "{KEYNOTE-407 Investigators} and Luis Paz-Ares and Alexander Luft and David Vicente and Ali Tafreshi and Mahmut G{\"u}m{\"u}ş and Julien Mazi{\`e}res and Barbara Hermes and {{\cC}ay Şenler}, Filiz and Tibor Csőszi and Andrea F{\"u}l{\"o}p and Jer{\'o}nimo Rodr{\'i}guez-Cid and Jonathan Wilson and Shunichi Sugawara and Terufumi Kato and Lee, {Ki Hyeong} and Ying Cheng and Silvia Novello and Balazs Halmos and Xiaodong Li and Lubiniecki, {Gregory M.} and Bilal Piperdi and Kowalski, {Dariusz M.}",
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T1 - Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer

AU - KEYNOTE-407 Investigators

AU - Paz-Ares, Luis

AU - Luft, Alexander

AU - Vicente, David

AU - Tafreshi, Ali

AU - Gümüş, Mahmut

AU - Mazières, Julien

AU - Hermes, Barbara

AU - Çay Şenler, Filiz

AU - Csőszi, Tibor

AU - Fülöp, Andrea

AU - Rodríguez-Cid, Jerónimo

AU - Wilson, Jonathan

AU - Sugawara, Shunichi

AU - Kato, Terufumi

AU - Lee, Ki Hyeong

AU - Cheng, Ying

AU - Novello, Silvia

AU - Halmos, Balazs

AU - Li, Xiaodong

AU - Lubiniecki, Gregory M.

AU - Piperdi, Bilal

AU - Kowalski, Dariusz M.

PY - 2018/11/22

Y1 - 2018/11/22

N2 - BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. METHODS: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival. RESULTS: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%). CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

AB - BACKGROUND: Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC. METHODS: In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival. RESULTS: After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%). CONCLUSIONS: In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

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JF - New England Journal of Medicine

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