Pembrolizumab for the treatment of non-small-cell lung cancer
Edward B Garon, Naiyer A Rizvi, Rina Hui, Natasha Leighl, Ani S Balmanoukian, Joseph Paul Eder, Amita Patnaik, Charu Aggarwal, Matthew Gubens, Leora Horn, Enric Carcereny, Myung-Ju Ahn, Enriqueta Felip, Jong-Seok Lee, Matthew D Hellmann, Omid Hamid, Jonathan W Goldman, Jean-Charles Soria, Marisa Dolled-Filhart, Ruth Z Rutledge, Jin Zhang, Jared K Lunceford, Reshma Rangwala, Gregory M Lubiniecki, Charlotte Roach, Kenneth Emancipator, Leena Gandhi, KEYNOTE-001 Investigators, Rina Hui, Quincy Chu, Natasha Leighl, François Chomy, Eric Dansin, Herve Lena, Gilles Quere, Jean-Charles Soria, Frederico Cappuzzo, Marina Garassino, Barbara Melotti, Alessandro Morabito, Daniele Santini, Paal Brunsvig, Øystein Fløtten, Myung-Ju Ahn, Dae Ho Lee, Jong-Seok Lee, Enric Carcereny, Enriqueta Felip, Amelia Insa, James Chih-Hsin Yang, Chun-Ming Tsai, Hendrick-Tobias Arkenau, Simon Grummet, Gary Middleton, Charu Aggarwal, Ani S Balmanoukian, Alberto Bessudo, George R Blumenschein Jr, Roxana Dronca, Joseph Paul Eder, Edward B Garon, Leena Gandhi, Jonathan Goldman, Matthew Gubens, Steven Hager, Omid Hamid, Matthew D Hellmann, Leora Horn, Elizabeth Johnson, Steven O'Day, Amita Patnaik, Suresh Ramalingam, Naiyer A Rizvi, Helen Ross, Mark Socinski, Edward B Garon, Naiyer A Rizvi, Rina Hui, Natasha Leighl, Ani S Balmanoukian, Joseph Paul Eder, Amita Patnaik, Charu Aggarwal, Matthew Gubens, Leora Horn, Enric Carcereny, Myung-Ju Ahn, Enriqueta Felip, Jong-Seok Lee, Matthew D Hellmann, Omid Hamid, Jonathan W Goldman, Jean-Charles Soria, Marisa Dolled-Filhart, Ruth Z Rutledge, Jin Zhang, Jared K Lunceford, Reshma Rangwala, Gregory M Lubiniecki, Charlotte Roach, Kenneth Emancipator, Leena Gandhi, KEYNOTE-001 Investigators, Rina Hui, Quincy Chu, Natasha Leighl, François Chomy, Eric Dansin, Herve Lena, Gilles Quere, Jean-Charles Soria, Frederico Cappuzzo, Marina Garassino, Barbara Melotti, Alessandro Morabito, Daniele Santini, Paal Brunsvig, Øystein Fløtten, Myung-Ju Ahn, Dae Ho Lee, Jong-Seok Lee, Enric Carcereny, Enriqueta Felip, Amelia Insa, James Chih-Hsin Yang, Chun-Ming Tsai, Hendrick-Tobias Arkenau, Simon Grummet, Gary Middleton, Charu Aggarwal, Ani S Balmanoukian, Alberto Bessudo, George R Blumenschein Jr, Roxana Dronca, Joseph Paul Eder, Edward B Garon, Leena Gandhi, Jonathan Goldman, Matthew Gubens, Steven Hager, Omid Hamid, Matthew D Hellmann, Leora Horn, Elizabeth Johnson, Steven O'Day, Amita Patnaik, Suresh Ramalingam, Naiyer A Rizvi, Helen Ross, Mark Socinski
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. (Funded by Merck; KEYNOTE-001 ClinicalTrials.gov number, NCT01295827.).
Source: PubMed