Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Martin Reck, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A Leiby, Gregory M Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R Brahmer, KEYNOTE-024 Investigators, George Kannourakis, Christopher Steer, Vinod Ganju, Kenneth O’Byrne, Ali Tafreshi, Rina Hui, Otto Burghuber, Paul Germonpre, Marc Lambrechts, Andrew Robinson, Michael Smylie, Vera Hirsh, Radj Gervais, Maurice Perol, Jaafar Bennouna, Damien Pouessel, Martin Reck, Georg Kopp, Peter Brossart, Thomas C Wehler, Ernst Spaeth-Schwalbe, Lajos Molnar, Beatrix Balint, Zsolt Papai-Szekely, Tibor Csoszi, Andrea Fulop, Szabolcs Soter, Zsuzsanna Szalai, Sandor Tehenes, Seamus O’Reilly, Linda Coate, Sinead Cuffe, Maya Gottfried, Nir Peled, Mirjana Wollner, Yair Bar, Shmuel Ariad, Ofer Merimsky, Giacomo Carteni, Paolo Bidoli, Cesare Gridelli, Paolo Marchetti, Marcello Tiseo, Marina Chiara Garassino, Laura Bonanno, Francesco Grossi, Filippo De Marinis, Andrea Ardizzoni, Atsushi Horiike, Miyako Satouchi, Nobuyuki Katakami, Akimasa Sekine, Yoshitaro Torii, Kazuhiko Nakagawa, Isamu Okamoto, Makoto Maemondo, Shigeki Umemura, Kaname Nosaki, Hideo Saka, Keisuke Aoe, Katsuyuki Hotta, Hiroshi Sakai, Shunichi Sugawara, Toshiaki Takahashi, Kazuma Kishi, Nobuyuki Yamamoto, Joop de Langen, Richard Sullivan, Maria Gracia Garcia Campelo, Oscar Juan Vidal, Reyes Bernabe Caro, Belen Rubio Viqueira, Manuel Domine Gomez, Delvys Rodriguez-Abreu, Enriqueta Felip, Marianne Nicolson, Rohit Lal, Dean A Fennel, Vanessa Potter, Gary Middleton, Mary E O’Brien, Christian Ottensmeir, Raffaele Califano, Jitendra Gandhi, Hassan I Tahsildar, Michael J Guarino, Ravidranath Patel, Konstantin Dragnev, Giuseppe Giaccone, Suman Rao, Eric Avery, Rachel Sanborn, William Eyre Lawler, Kartik Konduri, Francisco Robert, Jonathan Riess, Edward B Garon, Ticiana B Leal, Daniel Morgensztern, Harish Ahuja, Ari M Vanderwalde, Sonia E Reichert, Paul A Bun Jr, Robert Pirker, Weichung Shih, Martin Reck, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A Leiby, Gregory M Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R Brahmer, KEYNOTE-024 Investigators, George Kannourakis, Christopher Steer, Vinod Ganju, Kenneth O’Byrne, Ali Tafreshi, Rina Hui, Otto Burghuber, Paul Germonpre, Marc Lambrechts, Andrew Robinson, Michael Smylie, Vera Hirsh, Radj Gervais, Maurice Perol, Jaafar Bennouna, Damien Pouessel, Martin Reck, Georg Kopp, Peter Brossart, Thomas C Wehler, Ernst Spaeth-Schwalbe, Lajos Molnar, Beatrix Balint, Zsolt Papai-Szekely, Tibor Csoszi, Andrea Fulop, Szabolcs Soter, Zsuzsanna Szalai, Sandor Tehenes, Seamus O’Reilly, Linda Coate, Sinead Cuffe, Maya Gottfried, Nir Peled, Mirjana Wollner, Yair Bar, Shmuel Ariad, Ofer Merimsky, Giacomo Carteni, Paolo Bidoli, Cesare Gridelli, Paolo Marchetti, Marcello Tiseo, Marina Chiara Garassino, Laura Bonanno, Francesco Grossi, Filippo De Marinis, Andrea Ardizzoni, Atsushi Horiike, Miyako Satouchi, Nobuyuki Katakami, Akimasa Sekine, Yoshitaro Torii, Kazuhiko Nakagawa, Isamu Okamoto, Makoto Maemondo, Shigeki Umemura, Kaname Nosaki, Hideo Saka, Keisuke Aoe, Katsuyuki Hotta, Hiroshi Sakai, Shunichi Sugawara, Toshiaki Takahashi, Kazuma Kishi, Nobuyuki Yamamoto, Joop de Langen, Richard Sullivan, Maria Gracia Garcia Campelo, Oscar Juan Vidal, Reyes Bernabe Caro, Belen Rubio Viqueira, Manuel Domine Gomez, Delvys Rodriguez-Abreu, Enriqueta Felip, Marianne Nicolson, Rohit Lal, Dean A Fennel, Vanessa Potter, Gary Middleton, Mary E O’Brien, Christian Ottensmeir, Raffaele Califano, Jitendra Gandhi, Hassan I Tahsildar, Michael J Guarino, Ravidranath Patel, Konstantin Dragnev, Giuseppe Giaccone, Suman Rao, Eric Avery, Rachel Sanborn, William Eyre Lawler, Kartik Konduri, Francisco Robert, Jonathan Riess, Edward B Garon, Ticiana B Leal, Daniel Morgensztern, Harish Ahuja, Ari M Vanderwalde, Sonia E Reichert, Paul A Bun Jr, Robert Pirker, Weichung Shih
Abstract
Background: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
Methods: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.
Results: Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).
Conclusions: In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).
Source: PubMed