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BIBTEX RIS

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

2019; Elsevier BV; Volume: 393; Issue: 10183 Linguagem: Inglês

10.1016/s0140-6736(18)32409-7

1474-547X

Tony Mok, Yi‐Long Wu, Iveta Kudaba, Dariusz M. Kowalski, Byoung Chul Cho, H.Z. Turna, Gilberto de Castro, Vichien Srimuninnimit, К. К. Лактионов, Igor Bondarenko, Kaoru Kubota, Gregory M. Lubiniecki, Jin Zhang, Debra Kush, Gilberto Lopes, Grigory Adamchuk, Myung‐Ju Ahn, Aurelia Alexandru, Özden Altundağ, Anna Alyasova, Orest Andrusenko, Keisuke Aoe, António Araújo, Osvaldo Rudy Aren, Óscar Arrieta, Touch Ativitavas, Oscar Avendaño, Fernando Barata, Carlos H. Barrios, Carlos Beato, Per Bergström, Daniel Betticher, Л. В. Болотина, Igor Bondarenko, Michiel Botha, Sayeuri Buddu, Christian Caglevic, Andrés F. Cardona, Gilberto de Castro, Hugo R. Castro, Filiz Çay Şenler, Carlos Alexandre Sydow Cerny, Alvydas Česas, Gee-Chen Chan, Jianhua Chang, Gongyan Chen, Xi Chen, Susanna Cheng, Ying Cheng, Nelly Cherciu, Chao‐Hua Chiu, Byoung Chul Cho, Saulius Cicėnas, Daniel Ciurescu, Graham Cohen, Marcos André Costa, Pongwut Danchaivijitr, Flávia De Angelis, Sérgio Jobim Azevedo, Mircea Dediu, Tsvetan Deliverski, Pedro Rafael Martins De Marchi, F Vallés, Zhenyu Ding, Boyan Doganov, Lydia Dreosti, Ricardo Duarte, Regina Edusma-Dy, S. A. Emelyanov, Mustafa Erman, Yun Fan, Luis Fein, Jifeng Feng, David Fenton, Gustavo dos Santos Fernandes, Carlos Gil Ferreira, Fábio Franke, H. Freitas, Yasuhito Fujisaka, Héctor Galindo, Christina Galvez, Doina Ganea, Nuno Gil, Gustavo Girotto, Erdem Göker, Tuncay Göksel, Gonzalo Gomez Aubin, Luis Gomez Wolff, Håkan Griph, Mahmut Gümüş, Jacqueline A. Hall, Gregory Hart, Libor Havel, Jianxing He, Yong He, Carlos Hernández Hernández, Venceslau Hespanhol, Tomonori Hirashima, Chung Man James Ho, Atsushi Horiike, Yukio Hosomi, Katsuyuki Hotta, Mei Hou, Soon Hin How, Te‐Chun Hsia, Yi Hu, Masao Ichiki, Fumio Imamura, О. І. Іващук, Yasuo Iwamoto, Jana Jaal, Jacek Jassem, Christa Jordaan, Rosalyn A. Juergens, Diego Kaen, Ewa Kalinka‐Warzocha, Nina Karaseva, Bogusława Karaszewska, Andrzej Każarnowicz, Kazuo Kasahara, Nobuyuki Katakami, Terufumi Kato, Tomoya Kawaguchi, Joo Hang Kim, Kazuma Kishi, Vı́tězslav Kolek, Marchela Koleva, Petr Kolman, Leona Koubková, Rubén Dario Kowalyszyn, Dariusz M. Kowalski, Krassimir Koynov, Doran Ksienski, Kaoru Kubota, Iveta Kudaba, Takayasu Kurata, Gerli Kuusk, Lyudmila Kuzina, Ibolya Laczó, Guia Elena Imelda Ladrera, К. К. Лактионов, Gregory Landers, Sergey Lazarev, Guillermo Lerzo, Krzysztof Lesniewski- Kmak, Wei Li, Chong Kin Liam, Igor Lifirenko, O. N. Lipatov, Xiaoqing Liu, Zhe Liu, Sing Hung Lo, Valéria Lopes, Karla Alejandra Lopez, Shun Lü, Gastón L. Martinengo, Luís Más, Marina Matrosova, Rumyana Micheva, Zhasmina Mihaylova Milanova, Lucian Miron, Tony Mok, Matias Molina, Shuji Murakami, Yasuharu Nakahara, Tien Quang Nguyen, Takashi Nishimura, Adrian F. Ochsenbein, Tatsuo Ohira, R. Öhman, Byoung Chul Cho, Gyula Ostoros, Xuenong Ouyang, Е. Г. Овчинникова, Özgür Özyılkan, Luboš Petruželka, Xuan Dung Pham, Pablo Picon, Béla Pikó, Artem Poltoratsky, Olga Ponomarova, Patrice Popelková, Gunta Purkalne, Shukui Qin, Rodryg Ramlau, Bernardo Rappaport, Felipe Rey, Eduardo Richardet, Jaromı́r Roubec, Paul Ruff, Andrii Rusyn, Hideo Saka, Jorge Salas, Mario Sandoval, Lucas Vieira dos Santos, Toshiyuki Sawa, Kasan Seetalarom, Mesut Şeker, Nobuhiko Seki, Freddy Seolwane, Lucinda Shepherd, Sergii Shevnya, Andrea Kazumi Shimada, Yaroslav Shparyk, Ivan Sinielnikov, Daniela Sîrbu, Òren Smaletz, João Paulo Holanda Soares, Aumkhae Sookprasert, Giovanna Speranza, Vichien Srimuninnimit, Virote Sriuranpong, Zinaida Stara, Wu‐Chou Su, Shunichi Sugawara, Waldemar Szpak, Kazuhisa Takahashi, Nagio Takigawa, Hiroshi Tanaka, Jerry Tan Chun Bing, Qiyou Tang, Pavel Taranov, Hermes Tejada, Lye Mun Tho, Yoshitaro Torii, Dmytro Trukhyn, Maria Turdean, Hande Turna, G. Ursol, J Vaňásek, Mirta Varela, Marcela Vallejo, L. Vera, Ana-Paula Victorino, Tomáš Vlásek, Ihor Vynnychenko, Buhai Wang, Jie Wang, Kai Wang, Yi‐Long Wu, Kazuhiko Yamada, James Chih‐Hsin Yang, Takuma Yokoyama, Toshihide Yokoyama, Hiroshige Yoshioka, Perran Fulden Yumuk, Ángela R. Zambrano, Juan José Zarbá, Oleg Zarubenkov, Marius Žemaitis, Li Zhang, Li Zhang, Xin Zhang, Jun Zhao, Caicun Zhou, Jianying Zhou, Qing Zhou, Alfred Zippelius,

Lung Cancer Diagnosis and Treatment

First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894.From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.Merck Sharp & Dohme.