Pembrolizumab for the treatment of non-small-cell lung cancer

KEYNOTE-001 Investigators

Research output: Contribution to journalArticle

2603 Citations (Scopus)

Abstract

BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

Original languageEnglish
Pages (from-to)2018-2028
Number of pages11
JournalNew England Journal of Medicine
Volume372
Issue number21
DOIs
StatePublished - 21 May 2015

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Non-Small Cell Lung Carcinoma
Ligands
Therapeutics
CD274 Antigen
Disease-Free Survival
Neoplasms
Survival
pembrolizumab
Appetite
Pruritus
Fatigue
Appointments and Schedules
Cell Death
Body Weight
Staining and Labeling
Safety

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KEYNOTE-001 Investigators. / Pembrolizumab for the treatment of non-small-cell lung cancer. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 21. pp. 2018-2028.
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abstract = "BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4{\%}, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50{\%} of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50{\%} in the validation group, the response rate was 45.2{\%}. Among all the patients with a proportion score of at least 50{\%}, median progression-free survival was 6.3 months; median overall survival was not reached. CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50{\%} of tumor cells correlated with improved efficacy of pembrolizumab.",
author = "{KEYNOTE-001 Investigators} and Garon, {Edward B.} and Rizvi, {Naiyer A.} and Rina Hui and Natasha Leighl and Balmanoukian, {Ani S.} and Eder, {Joseph Paul} and Amita Patnaik and Charu Aggarwal and Matthew Gubens and Leora Horn and Enric Carcereny and Ahn, {Myung Ju} and Enriqueta Felip and Lee, {Jong Seok} and Hellmann, {Matthew D.} and Omid Hamid and Goldman, {Jonathan W.} and Soria, {Jean Charles} and Marisa Dolled-Filhart and Rutledge, {Ruth Z.} and Jin Zhang and Lunceford, {Jared K.} and Reshma Rangwala and Lubiniecki, {Gregory M.} and Charlotte Roach and Kenneth Emancipator and Leena Gandhi",
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Pembrolizumab for the treatment of non-small-cell lung cancer. / KEYNOTE-001 Investigators.

In: New England Journal of Medicine, Vol. 372, No. 21, 21.05.2015, p. 2018-2028.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pembrolizumab for the treatment of non-small-cell lung cancer

AU - KEYNOTE-001 Investigators

AU - Garon, Edward B.

AU - Rizvi, Naiyer A.

AU - Hui, Rina

AU - Leighl, Natasha

AU - Balmanoukian, Ani S.

AU - Eder, Joseph Paul

AU - Patnaik, Amita

AU - Aggarwal, Charu

AU - Gubens, Matthew

AU - Horn, Leora

AU - Carcereny, Enric

AU - Ahn, Myung Ju

AU - Felip, Enriqueta

AU - Lee, Jong Seok

AU - Hellmann, Matthew D.

AU - Hamid, Omid

AU - Goldman, Jonathan W.

AU - Soria, Jean Charles

AU - Dolled-Filhart, Marisa

AU - Rutledge, Ruth Z.

AU - Zhang, Jin

AU - Lunceford, Jared K.

AU - Rangwala, Reshma

AU - Lubiniecki, Gregory M.

AU - Roach, Charlotte

AU - Emancipator, Kenneth

AU - Gandhi, Leena

PY - 2015/5/21

Y1 - 2015/5/21

N2 - BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

AB - BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

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U2 - 10.1056/NEJMoa1501824

DO - 10.1056/NEJMoa1501824

M3 - Article

C2 - 25891174

AN - SCOPUS:84929481480

VL - 372

SP - 2018

EP - 2028

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -