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

Tony S.K. Mok, Yi Long Wu, Iveta Kudaba, Dariusz M. Kowalski, Byoung Chul Cho, Hande Z. Turna, Gilberto Castro, Vichien Srimuninnimit, Konstantin K. Laktionov, Igor Bondarenko, Kaoru Kubota, Gregory M. Lubiniecki, Jin Zhang, Debra Kush, Gilberto Lopes, Gonzalo Gomez Aubin, Luis Fein, Diego Kaen, Ruben Kowalyszyn, Guillermo LerzoGaston Martinengo, Matias Molina, Eduardo Richardet, Pablo Picon, Mirta Varela, Juan Jose Zarba, Sergio Jobim de Azevedo, Carlos Henrique Barrios, Carlos Beato, Carlos Alexandre Sydow Cerny, Pedro Rafael Martins De Marchi, Gustavo Fernandes, Fabio Andre Franke, Helano Freitas, Gustavo Girotto, Valeria Lopes, Lucas Santos, Marcos Andre Costa, Andrea Kazumi Shimada, Oren Smaletz, Joao Paulo Holanda Soares, Ana Paula Victorino, Carlos Ferreira, Marchela Koleva, Krassimir Koynov, Rumyana Micheva, Tsvetan Deliverski, Zhasmina Milanova, Boyan Doganov, Susanna Cheng, Flavia De Angelis, Giovanna Speranza, Rosalyn Anne Juergens, Doran Ksienski, David Fenton, Osvaldo Aren, Christian Caglevic, Hector Galindo, Felipe Rey, Jianhua Chang, Gongyan Chen, Xi Chen, Xuenong Ouyang, Ying Cheng, Zhenyu Ding, Mei Hou, Yun Fan, Jifeng Feng, Jianxing He, Yong He, Yi Hu, Wei Li, Xiaoqing Liu, Zhe Liu, Shun Lu, Shukui Qin, Qiyou Tang, Buhai Wang, Kai Wang, Li Zhang, Xin Zhang, Jun Zhao, Jie Wang, Caicun Zhou, Jianying Zhou, Qing Zhou, Yilong Wu, Andres Cardona, Ricardo Duarte, Luis Gomez Wolff, Angela Zambrano, Marcela Vallejo, Libor Havel, Vitezslav Kolek, Petr Kolman, Leona Koubkova, Lubos Petruzelka, Patrice Popelkova, Jaromir Roubec, Jaroslav Vanasek, Tomas Vlasek, Jana Jaal, Gerli Kuusk, Oscar Avendano, Hugo Castro, Karla Lopez, Mario Sandoval, Chung Man James Ho, Sing Hung Lo, Ibolya Laczo, Bela Piko, Gyula Ostoros, Keisuke Aoe, Yasuhito Fujisaka, Tomonori Hirashima, Atsushi Horiike, Yukio Hosomi, Katsuyuki Hotta, Masao Ichiki, Fumio Imamura, Yasuo Iwamoto, Kazuo Kasahara, Nobuyuki Katakami, Terufumi Kato, Shuji Murakami, Tomoya Kawaguchi, Kazuma Kishi, Kaoru Kubota, Takayasu Kurata, Yoshitaro Torii, Yasuharu Nakahara, Takashi Nishimura, Tatsuo Ohira, Hideo Saka, Toshiyuki Sawa, Nobuhiko Seki, Shunichi Sugawara, Kazuhisa Takahashi, Nagio Takigawa, Hiroshi Tanaka, Kazuhiko Yamada, Takuma Yokoyama, Toshihide Yokoyama, Hiroshige Yoshioka, Iveta Kudaba, Gunta Purkalne, Zinaida Stara, Alvydas Cesas, Saulius Cicenas, Marius Zemaitis, Soon Hin How, Chong Kin Liam, Choo Khoon Ong, Lye Mun Tho, Oscar Arrieta Rodriguez, Flor de The Bustamante Valles, Carlos Hernandez Hernandez, Luis Mas, Luis Vera, Jorge Salas, Hermes Tejada, Regina Edusma-Dy, Christina Galvez, Guia Elena Imelda Ladrera, Jerry Tan Chun Bing, Jacek Jassem, Ewa Kalinka-Warzocha, Boguslawa Karaszewska, Andrzej Kazarnowicz, Dariusz Kowalski, Krzysztof Lesniewski Kmak, Rodryg Ramlau, Antonio Araujo, Fernando Barata, Nuno Gil, Venceslau Hespanhol, Aurelia Alexandru, Mircea Dediu, Nelly Cherciu, Daniel Ciurescu, Doina Ganea, Lucian Miron, Daniela Sirbu, Maria Turdean, Sergey Emelyanov, Nina Karaseva, Lyudmila Kuzina, Sergey Lazarev, Igor Lifirenko, Larisa Bolotina, Oleg Lipatov, Elena Ovchinnikova, Marina Matrosova, Anna Alyasova, Artem Poltoratsky, Pavel Taranov, Oleg Zarubenkov, Graham Cohen, Lydia Dreosti, Freddy Seolwane, Jacqueline Hall, Gregory Hart, Christa Jordaan, Sayeuri Buddu, Michiel Botha, Gregory Landers, Bernardo Rappaport, Paul Ruff, Lucinda Shepherd, Waldemar Szpak, Myung Ju Ahn, Byoung Chul Cho, Joo Hang Kim, Per Bergstrom, Ronny Ohman, Hakan Griph, Daniel Betticher, Adrian Ochsenbein, Alfred Zippelius, Gee Chen Chan, Chao Hua Chiu, Te Chun Hsia, Wu Chou Su, Chih Hsin Yang, Touch Ativitavas, Pongwut Danchaivijitr, Vichien Srimuninnimit, Kasan Seetalarom, Aumkhae Sookprasert, Virote Sriuranpong, Ozden Altundag, Filiz Cay Senler, Mustafa Erman, Tuncay Goksel, Erdem Goker, Ozgur Ozyilkan, Mesut Seker, Mahmut Gumus, Hande Turna, Fulden Yumuk, Grigory Adamchuk, Igor Bondarenko, Oleksandr Ivashchuk, Olga Ponomarova, Andrii Rusyn, Sergii Shevnya, Yaroslav Shparyk, Ivan Sinielnikov, Orest Andrusenko, Dmytro Trukhyn, Grygoriy Ursol, Ihor Vynnychenko, Tien Quang Nguyen, Xuan Dung Pham, Gilberto Castro, Kaoru Kubota

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Abstract

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme.

Original languageEnglish
Pages (from-to)1819-1830
Number of pages12
JournalThe Lancet
Volume393
Issue number10183
DOIs
Publication statusPublished - 2019 May 4

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Non-Small Cell Lung Carcinoma
Ligands
Drug Therapy
Neoplasms
Population
Survival
pembrolizumab
Far East
Random Allocation
Life Expectancy
Platinum
Disease-Free Survival
Histology
Therapeutics
Research Personnel
Mutation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Mok, Tony S.K. ; Wu, Yi Long ; Kudaba, Iveta ; Kowalski, Dariusz M. ; Cho, Byoung Chul ; Turna, Hande Z. ; Castro, Gilberto ; Srimuninnimit, Vichien ; Laktionov, Konstantin K. ; Bondarenko, Igor ; Kubota, Kaoru ; Lubiniecki, Gregory M. ; Zhang, Jin ; Kush, Debra ; Lopes, Gilberto ; Gomez Aubin, Gonzalo ; Fein, Luis ; Kaen, Diego ; Kowalyszyn, Ruben ; Lerzo, Guillermo ; Martinengo, Gaston ; Molina, Matias ; Richardet, Eduardo ; Picon, Pablo ; Varela, Mirta ; Zarba, Juan Jose ; de Azevedo, Sergio Jobim ; Barrios, Carlos Henrique ; Beato, Carlos ; Cerny, Carlos Alexandre Sydow ; De Marchi, Pedro Rafael Martins ; Fernandes, Gustavo ; Franke, Fabio Andre ; Freitas, Helano ; Girotto, Gustavo ; Lopes, Valeria ; Santos, Lucas ; Costa, Marcos Andre ; Shimada, Andrea Kazumi ; Smaletz, Oren ; Soares, Joao Paulo Holanda ; Victorino, Ana Paula ; Ferreira, Carlos ; Koleva, Marchela ; Koynov, Krassimir ; Micheva, Rumyana ; Deliverski, Tsvetan ; Milanova, Zhasmina ; Doganov, Boyan ; Cheng, Susanna ; De Angelis, Flavia ; Speranza, Giovanna ; Juergens, Rosalyn Anne ; Ksienski, Doran ; Fenton, David ; Aren, Osvaldo ; Caglevic, Christian ; Galindo, Hector ; Rey, Felipe ; Chang, Jianhua ; Chen, Gongyan ; Chen, Xi ; Ouyang, Xuenong ; Cheng, Ying ; Ding, Zhenyu ; Hou, Mei ; Fan, Yun ; Feng, Jifeng ; He, Jianxing ; He, Yong ; Hu, Yi ; Li, Wei ; Liu, Xiaoqing ; Liu, Zhe ; Lu, Shun ; Qin, Shukui ; Tang, Qiyou ; Wang, Buhai ; Wang, Kai ; Zhang, Li ; Zhang, Xin ; Zhao, Jun ; Wang, Jie ; Zhou, Caicun ; Zhou, Jianying ; Zhou, Qing ; Wu, Yilong ; Cardona, Andres ; Duarte, Ricardo ; Gomez Wolff, Luis ; Zambrano, Angela ; Vallejo, Marcela ; Havel, Libor ; Kolek, Vitezslav ; Kolman, Petr ; Koubkova, Leona ; Petruzelka, Lubos ; Popelkova, Patrice ; Roubec, Jaromir ; Vanasek, Jaroslav ; Vlasek, Tomas ; Jaal, Jana ; Kuusk, Gerli ; Avendano, Oscar ; Castro, Hugo ; Lopez, Karla ; Sandoval, Mario ; Ho, Chung Man James ; Lo, Sing Hung ; Laczo, Ibolya ; Piko, Bela ; Ostoros, Gyula ; Aoe, Keisuke ; Fujisaka, Yasuhito ; Hirashima, Tomonori ; Horiike, Atsushi ; Hosomi, Yukio ; Hotta, Katsuyuki ; Ichiki, Masao ; Imamura, Fumio ; Iwamoto, Yasuo ; Kasahara, Kazuo ; Katakami, Nobuyuki ; Kato, Terufumi ; Murakami, Shuji ; Kawaguchi, Tomoya ; Kishi, Kazuma ; Kubota, Kaoru ; Kurata, Takayasu ; Torii, Yoshitaro ; Nakahara, Yasuharu ; Nishimura, Takashi ; Ohira, Tatsuo ; Saka, Hideo ; Sawa, Toshiyuki ; Seki, Nobuhiko ; Sugawara, Shunichi ; Takahashi, Kazuhisa ; Takigawa, Nagio ; Tanaka, Hiroshi ; Yamada, Kazuhiko ; Yokoyama, Takuma ; Yokoyama, Toshihide ; Yoshioka, Hiroshige ; Kudaba, Iveta ; Purkalne, Gunta ; Stara, Zinaida ; Cesas, Alvydas ; Cicenas, Saulius ; Zemaitis, Marius ; How, Soon Hin ; Liam, Chong Kin ; Ong, Choo Khoon ; Tho, Lye Mun ; Arrieta Rodriguez, Oscar ; de The Bustamante Valles, Flor ; Hernandez Hernandez, Carlos ; Mas, Luis ; Vera, Luis ; Salas, Jorge ; Tejada, Hermes ; Edusma-Dy, Regina ; Galvez, Christina ; Ladrera, Guia Elena Imelda ; Tan Chun Bing, Jerry ; Jassem, Jacek ; Kalinka-Warzocha, Ewa ; Karaszewska, Boguslawa ; Kazarnowicz, Andrzej ; Kowalski, Dariusz ; Lesniewski Kmak, Krzysztof ; Ramlau, Rodryg ; Araujo, Antonio ; Barata, Fernando ; Gil, Nuno ; Hespanhol, Venceslau ; Alexandru, Aurelia ; Dediu, Mircea ; Cherciu, Nelly ; Ciurescu, Daniel ; Ganea, Doina ; Miron, Lucian ; Sirbu, Daniela ; Turdean, Maria ; Emelyanov, Sergey ; Karaseva, Nina ; Kuzina, Lyudmila ; Lazarev, Sergey ; Lifirenko, Igor ; Bolotina, Larisa ; Lipatov, Oleg ; Ovchinnikova, Elena ; Matrosova, Marina ; Alyasova, Anna ; Poltoratsky, Artem ; Taranov, Pavel ; Zarubenkov, Oleg ; Cohen, Graham ; Dreosti, Lydia ; Seolwane, Freddy ; Hall, Jacqueline ; Hart, Gregory ; Jordaan, Christa ; Buddu, Sayeuri ; Botha, Michiel ; Landers, Gregory ; Rappaport, Bernardo ; Ruff, Paul ; Shepherd, Lucinda ; Szpak, Waldemar ; Ahn, Myung Ju ; Cho, Byoung Chul ; Kim, Joo Hang ; Bergstrom, Per ; Ohman, Ronny ; Griph, Hakan ; Betticher, Daniel ; Ochsenbein, Adrian ; Zippelius, Alfred ; Chan, Gee Chen ; Chiu, Chao Hua ; Hsia, Te Chun ; Su, Wu Chou ; Yang, Chih Hsin ; Ativitavas, Touch ; Danchaivijitr, Pongwut ; Srimuninnimit, Vichien ; Seetalarom, Kasan ; Sookprasert, Aumkhae ; Sriuranpong, Virote ; Altundag, Ozden ; Cay Senler, Filiz ; Erman, Mustafa ; Goksel, Tuncay ; Goker, Erdem ; Ozyilkan, Ozgur ; Seker, Mesut ; Gumus, Mahmut ; Turna, Hande ; Yumuk, Fulden ; Adamchuk, Grigory ; Bondarenko, Igor ; Ivashchuk, Oleksandr ; Ponomarova, Olga ; Rusyn, Andrii ; Shevnya, Sergii ; Shparyk, Yaroslav ; Sinielnikov, Ivan ; Andrusenko, Orest ; Trukhyn, Dmytro ; Ursol, Grygoriy ; Vynnychenko, Ihor ; Nguyen, Tien Quang ; Pham, Xuan Dung ; Castro, Gilberto ; Kubota, Kaoru. / 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. In: The Lancet. 2019 ; Vol. 393, No. 10183. pp. 1819-1830.
@article{14a6fc3e212a44329e46d4740d1c793e,
title = "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",
abstract = "Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme.",
author = "Mok, {Tony S.K.} and Wu, {Yi Long} and Iveta Kudaba and Kowalski, {Dariusz M.} and Cho, {Byoung Chul} and Turna, {Hande Z.} and Gilberto Castro and Vichien Srimuninnimit and Laktionov, {Konstantin K.} and Igor Bondarenko and Kaoru Kubota and Lubiniecki, {Gregory M.} and Jin Zhang and Debra Kush and Gilberto Lopes and {Gomez Aubin}, Gonzalo and Luis Fein and Diego Kaen and Ruben Kowalyszyn and Guillermo Lerzo and Gaston Martinengo and Matias Molina and Eduardo Richardet and Pablo Picon and Mirta Varela and Zarba, {Juan Jose} and {de Azevedo}, {Sergio Jobim} and Barrios, {Carlos Henrique} and Carlos Beato and Cerny, {Carlos Alexandre Sydow} and {De Marchi}, {Pedro Rafael Martins} and Gustavo Fernandes and Franke, {Fabio Andre} and Helano Freitas and Gustavo Girotto and Valeria Lopes and Lucas Santos and Costa, {Marcos Andre} and Shimada, {Andrea Kazumi} and Oren Smaletz and Soares, {Joao Paulo Holanda} and Victorino, {Ana Paula} and Carlos Ferreira and Marchela Koleva and Krassimir Koynov and Rumyana Micheva and Tsvetan Deliverski and Zhasmina Milanova and Boyan Doganov and Susanna Cheng and {De Angelis}, Flavia and Giovanna Speranza and Juergens, {Rosalyn Anne} and Doran Ksienski and David Fenton and Osvaldo Aren and Christian Caglevic and Hector Galindo and Felipe Rey and Jianhua Chang and Gongyan Chen and Xi Chen and Xuenong Ouyang and Ying Cheng and Zhenyu Ding and Mei Hou and Yun Fan and Jifeng Feng and Jianxing He and Yong He and Yi Hu and Wei Li and Xiaoqing Liu and Zhe Liu and Shun Lu and Shukui Qin and Qiyou Tang and Buhai Wang and Kai Wang and Li Zhang and Xin Zhang and Jun Zhao and Jie Wang and Caicun Zhou and Jianying Zhou and Qing Zhou and Yilong Wu and Andres Cardona and Ricardo Duarte and {Gomez Wolff}, Luis and Angela Zambrano and Marcela Vallejo and Libor Havel and Vitezslav Kolek and Petr Kolman and Leona Koubkova and Lubos Petruzelka and Patrice Popelkova and Jaromir Roubec and Jaroslav Vanasek and Tomas Vlasek and Jana Jaal and Gerli Kuusk and Oscar Avendano and Hugo Castro and Karla Lopez and Mario Sandoval and Ho, {Chung Man James} and Lo, {Sing Hung} and Ibolya Laczo and Bela Piko and Gyula Ostoros and Keisuke Aoe and Yasuhito Fujisaka and Tomonori Hirashima and Atsushi Horiike and Yukio Hosomi and Katsuyuki Hotta and Masao Ichiki and Fumio Imamura and Yasuo Iwamoto and Kazuo Kasahara and Nobuyuki Katakami and Terufumi Kato and Shuji Murakami and Tomoya Kawaguchi and Kazuma Kishi and Kaoru Kubota and Takayasu Kurata and Yoshitaro Torii and Yasuharu Nakahara and Takashi Nishimura and Tatsuo Ohira and Hideo Saka and Toshiyuki Sawa and Nobuhiko Seki and Shunichi Sugawara and Kazuhisa Takahashi and Nagio Takigawa and Hiroshi Tanaka and Kazuhiko Yamada and Takuma Yokoyama and Toshihide Yokoyama and Hiroshige Yoshioka and Iveta Kudaba and Gunta Purkalne and Zinaida Stara and Alvydas Cesas and Saulius Cicenas and Marius Zemaitis and How, {Soon Hin} and Liam, {Chong Kin} and Ong, {Choo Khoon} and Tho, {Lye Mun} and {Arrieta Rodriguez}, Oscar and {de The Bustamante Valles}, Flor and {Hernandez Hernandez}, Carlos and Luis Mas and Luis Vera and Jorge Salas and Hermes Tejada and Regina Edusma-Dy and Christina Galvez and Ladrera, {Guia Elena Imelda} and {Tan Chun Bing}, Jerry and Jacek Jassem and Ewa Kalinka-Warzocha and Boguslawa Karaszewska and Andrzej Kazarnowicz and Dariusz Kowalski and {Lesniewski Kmak}, Krzysztof and Rodryg Ramlau and Antonio Araujo and Fernando Barata and Nuno Gil and Venceslau Hespanhol and Aurelia Alexandru and Mircea Dediu and Nelly Cherciu and Daniel Ciurescu and Doina Ganea and Lucian Miron and Daniela Sirbu and Maria Turdean and Sergey Emelyanov and Nina Karaseva and Lyudmila Kuzina and Sergey Lazarev and Igor Lifirenko and Larisa Bolotina and Oleg Lipatov and Elena Ovchinnikova and Marina Matrosova and Anna Alyasova and Artem Poltoratsky and Pavel Taranov and Oleg Zarubenkov and Graham Cohen and Lydia Dreosti and Freddy Seolwane and Jacqueline Hall and Gregory Hart and Christa Jordaan and Sayeuri Buddu and Michiel Botha and Gregory Landers and Bernardo Rappaport and Paul Ruff and Lucinda Shepherd and Waldemar Szpak and Ahn, {Myung Ju} and Cho, {Byoung Chul} and Kim, {Joo Hang} and Per Bergstrom and Ronny Ohman and Hakan Griph and Daniel Betticher and Adrian Ochsenbein and Alfred Zippelius and Chan, {Gee Chen} and Chiu, {Chao Hua} and Hsia, {Te Chun} and Su, {Wu Chou} and Yang, {Chih Hsin} and Touch Ativitavas and Pongwut Danchaivijitr and Vichien Srimuninnimit and Kasan Seetalarom and Aumkhae Sookprasert and Virote Sriuranpong and Ozden Altundag and {Cay Senler}, Filiz and Mustafa Erman and Tuncay Goksel and Erdem Goker and Ozgur Ozyilkan and Mesut Seker and Mahmut Gumus and Hande Turna and Fulden Yumuk and Grigory Adamchuk and Igor Bondarenko and Oleksandr Ivashchuk and Olga Ponomarova and Andrii Rusyn and Sergii Shevnya and Yaroslav Shparyk and Ivan Sinielnikov and Orest Andrusenko and Dmytro Trukhyn and Grygoriy Ursol and Ihor Vynnychenko and Nguyen, {Tien Quang} and Pham, {Xuan Dung} and Gilberto Castro and Kaoru Kubota",
year = "2019",
month = "5",
day = "4",
doi = "10.1016/S0140-6736(18)32409-7",
language = "English",
volume = "393",
pages = "1819--1830",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "10183",

}

Mok, TSK, Wu, YL, Kudaba, I, Kowalski, DM, Cho, BC, Turna, HZ, Castro, G, Srimuninnimit, V, Laktionov, KK, Bondarenko, I, Kubota, K, Lubiniecki, GM, Zhang, J, Kush, D, Lopes, G, Gomez Aubin, G, Fein, L, Kaen, D, Kowalyszyn, R, Lerzo, G, Martinengo, G, Molina, M, Richardet, E, Picon, P, Varela, M, Zarba, JJ, de Azevedo, SJ, Barrios, CH, Beato, C, Cerny, CAS, De Marchi, PRM, Fernandes, G, Franke, FA, Freitas, H, Girotto, G, Lopes, V, Santos, L, Costa, MA, Shimada, AK, Smaletz, O, Soares, JPH, Victorino, AP, Ferreira, C, Koleva, M, Koynov, K, Micheva, R, Deliverski, T, Milanova, Z, Doganov, B, Cheng, S, De Angelis, F, Speranza, G, Juergens, RA, Ksienski, D, Fenton, D, Aren, O, Caglevic, C, Galindo, H, Rey, F, Chang, J, Chen, G, Chen, X, Ouyang, X, Cheng, Y, Ding, Z, Hou, M, Fan, Y, Feng, J, He, J, He, Y, Hu, Y, Li, W, Liu, X, Liu, Z, Lu, S, Qin, S, Tang, Q, Wang, B, Wang, K, Zhang, L, Zhang, X, Zhao, J, Wang, J, Zhou, C, Zhou, J, Zhou, Q, Wu, Y, Cardona, A, Duarte, R, Gomez Wolff, L, Zambrano, A, Vallejo, M, Havel, L, Kolek, V, Kolman, P, Koubkova, L, Petruzelka, L, Popelkova, P, Roubec, J, Vanasek, J, Vlasek, T, Jaal, J, Kuusk, G, Avendano, O, Castro, H, Lopez, K, Sandoval, M, Ho, CMJ, Lo, SH, Laczo, I, Piko, B, Ostoros, G, Aoe, K, Fujisaka, Y, Hirashima, T, Horiike, A, Hosomi, Y, Hotta, K, Ichiki, M, Imamura, F, Iwamoto, Y, Kasahara, K, Katakami, N, Kato, T, Murakami, S, Kawaguchi, T, Kishi, K, Kubota, K, Kurata, T, Torii, Y, Nakahara, Y, Nishimura, T, Ohira, T, Saka, H, Sawa, T, Seki, N, Sugawara, S, Takahashi, K, Takigawa, N, Tanaka, H, Yamada, K, Yokoyama, T, Yokoyama, T, Yoshioka, H, Kudaba, I, Purkalne, G, Stara, Z, Cesas, A, Cicenas, S, Zemaitis, M, How, SH, Liam, CK, Ong, CK, Tho, LM, Arrieta Rodriguez, O, de The Bustamante Valles, F, Hernandez Hernandez, C, Mas, L, Vera, L, Salas, J, Tejada, H, Edusma-Dy, R, Galvez, C, Ladrera, GEI, Tan Chun Bing, J, Jassem, J, Kalinka-Warzocha, E, Karaszewska, B, Kazarnowicz, A, Kowalski, D, Lesniewski Kmak, K, Ramlau, R, Araujo, A, Barata, F, Gil, N, Hespanhol, V, Alexandru, A, Dediu, M, Cherciu, N, Ciurescu, D, Ganea, D, Miron, L, Sirbu, D, Turdean, M, Emelyanov, S, Karaseva, N, Kuzina, L, Lazarev, S, Lifirenko, I, Bolotina, L, Lipatov, O, Ovchinnikova, E, Matrosova, M, Alyasova, A, Poltoratsky, A, Taranov, P, Zarubenkov, O, Cohen, G, Dreosti, L, Seolwane, F, Hall, J, Hart, G, Jordaan, C, Buddu, S, Botha, M, Landers, G, Rappaport, B, Ruff, P, Shepherd, L, Szpak, W, Ahn, MJ, Cho, BC, Kim, JH, Bergstrom, P, Ohman, R, Griph, H, Betticher, D, Ochsenbein, A, Zippelius, A, Chan, GC, Chiu, CH, Hsia, TC, Su, WC, Yang, CH, Ativitavas, T, Danchaivijitr, P, Srimuninnimit, V, Seetalarom, K, Sookprasert, A, Sriuranpong, V, Altundag, O, Cay Senler, F, Erman, M, Goksel, T, Goker, E, Ozyilkan, O, Seker, M, Gumus, M, Turna, H, Yumuk, F, Adamchuk, G, Bondarenko, I, Ivashchuk, O, Ponomarova, O, Rusyn, A, Shevnya, S, Shparyk, Y, Sinielnikov, I, Andrusenko, O, Trukhyn, D, Ursol, G, Vynnychenko, I, Nguyen, TQ, Pham, XD, Castro, G & Kubota, K 2019, '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', The Lancet, vol. 393, no. 10183, pp. 1819-1830. https://doi.org/10.1016/S0140-6736(18)32409-7

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. / Mok, Tony S.K.; Wu, Yi Long; Kudaba, Iveta; Kowalski, Dariusz M.; Cho, Byoung Chul; Turna, Hande Z.; Castro, Gilberto; Srimuninnimit, Vichien; Laktionov, Konstantin K.; Bondarenko, Igor; Kubota, Kaoru; Lubiniecki, Gregory M.; Zhang, Jin; Kush, Debra; Lopes, Gilberto; Gomez Aubin, Gonzalo; Fein, Luis; Kaen, Diego; Kowalyszyn, Ruben; Lerzo, Guillermo; Martinengo, Gaston; Molina, Matias; Richardet, Eduardo; Picon, Pablo; Varela, Mirta; Zarba, Juan Jose; de Azevedo, Sergio Jobim; Barrios, Carlos Henrique; Beato, Carlos; Cerny, Carlos Alexandre Sydow; De Marchi, Pedro Rafael Martins; Fernandes, Gustavo; Franke, Fabio Andre; Freitas, Helano; Girotto, Gustavo; Lopes, Valeria; Santos, Lucas; Costa, Marcos Andre; Shimada, Andrea Kazumi; Smaletz, Oren; Soares, Joao Paulo Holanda; Victorino, Ana Paula; Ferreira, Carlos; Koleva, Marchela; Koynov, Krassimir; Micheva, Rumyana; Deliverski, Tsvetan; Milanova, Zhasmina; Doganov, Boyan; Cheng, Susanna; De Angelis, Flavia; Speranza, Giovanna; Juergens, Rosalyn Anne; Ksienski, Doran; Fenton, David; Aren, Osvaldo; Caglevic, Christian; Galindo, Hector; Rey, Felipe; Chang, Jianhua; Chen, Gongyan; Chen, Xi; Ouyang, Xuenong; Cheng, Ying; Ding, Zhenyu; Hou, Mei; Fan, Yun; Feng, Jifeng; He, Jianxing; He, Yong; Hu, Yi; Li, Wei; Liu, Xiaoqing; Liu, Zhe; Lu, Shun; Qin, Shukui; Tang, Qiyou; Wang, Buhai; Wang, Kai; Zhang, Li; Zhang, Xin; Zhao, Jun; Wang, Jie; Zhou, Caicun; Zhou, Jianying; Zhou, Qing; Wu, Yilong; Cardona, Andres; Duarte, Ricardo; Gomez Wolff, Luis; Zambrano, Angela; Vallejo, Marcela; Havel, Libor; Kolek, Vitezslav; Kolman, Petr; Koubkova, Leona; Petruzelka, Lubos; Popelkova, Patrice; Roubec, Jaromir; Vanasek, Jaroslav; Vlasek, Tomas; Jaal, Jana; Kuusk, Gerli; Avendano, Oscar; Castro, Hugo; Lopez, Karla; Sandoval, Mario; Ho, Chung Man James; Lo, Sing Hung; Laczo, Ibolya; Piko, Bela; Ostoros, Gyula; Aoe, Keisuke; Fujisaka, Yasuhito; Hirashima, Tomonori; Horiike, Atsushi; Hosomi, Yukio; Hotta, Katsuyuki; Ichiki, Masao; Imamura, Fumio; Iwamoto, Yasuo; Kasahara, Kazuo; Katakami, Nobuyuki; Kato, Terufumi; Murakami, Shuji; Kawaguchi, Tomoya; Kishi, Kazuma; Kubota, Kaoru; Kurata, Takayasu; Torii, Yoshitaro; Nakahara, Yasuharu; Nishimura, Takashi; Ohira, Tatsuo; Saka, Hideo; Sawa, Toshiyuki; Seki, Nobuhiko; Sugawara, Shunichi; Takahashi, Kazuhisa; Takigawa, Nagio; Tanaka, Hiroshi; Yamada, Kazuhiko; Yokoyama, Takuma; Yokoyama, Toshihide; Yoshioka, Hiroshige; Kudaba, Iveta; Purkalne, Gunta; Stara, Zinaida; Cesas, Alvydas; Cicenas, Saulius; Zemaitis, Marius; How, Soon Hin; Liam, Chong Kin; Ong, Choo Khoon; Tho, Lye Mun; Arrieta Rodriguez, Oscar; de The Bustamante Valles, Flor; Hernandez Hernandez, Carlos; Mas, Luis; Vera, Luis; Salas, Jorge; Tejada, Hermes; Edusma-Dy, Regina; Galvez, Christina; Ladrera, Guia Elena Imelda; Tan Chun Bing, Jerry; Jassem, Jacek; Kalinka-Warzocha, Ewa; Karaszewska, Boguslawa; Kazarnowicz, Andrzej; Kowalski, Dariusz; Lesniewski Kmak, Krzysztof; Ramlau, Rodryg; Araujo, Antonio; Barata, Fernando; Gil, Nuno; Hespanhol, Venceslau; Alexandru, Aurelia; Dediu, Mircea; Cherciu, Nelly; Ciurescu, Daniel; Ganea, Doina; Miron, Lucian; Sirbu, Daniela; Turdean, Maria; Emelyanov, Sergey; Karaseva, Nina; Kuzina, Lyudmila; Lazarev, Sergey; Lifirenko, Igor; Bolotina, Larisa; Lipatov, Oleg; Ovchinnikova, Elena; Matrosova, Marina; Alyasova, Anna; Poltoratsky, Artem; Taranov, Pavel; Zarubenkov, Oleg; Cohen, Graham; Dreosti, Lydia; Seolwane, Freddy; Hall, Jacqueline; Hart, Gregory; Jordaan, Christa; Buddu, Sayeuri; Botha, Michiel; Landers, Gregory; Rappaport, Bernardo; Ruff, Paul; Shepherd, Lucinda; Szpak, Waldemar; Ahn, Myung Ju; Cho, Byoung Chul; Kim, Joo Hang; Bergstrom, Per; Ohman, Ronny; Griph, Hakan; Betticher, Daniel; Ochsenbein, Adrian; Zippelius, Alfred; Chan, Gee Chen; Chiu, Chao Hua; Hsia, Te Chun; Su, Wu Chou; Yang, Chih Hsin; Ativitavas, Touch; Danchaivijitr, Pongwut; Srimuninnimit, Vichien; Seetalarom, Kasan; Sookprasert, Aumkhae; Sriuranpong, Virote; Altundag, Ozden; Cay Senler, Filiz; Erman, Mustafa; Goksel, Tuncay; Goker, Erdem; Ozyilkan, Ozgur; Seker, Mesut; Gumus, Mahmut; Turna, Hande; Yumuk, Fulden; Adamchuk, Grigory; Bondarenko, Igor; Ivashchuk, Oleksandr; Ponomarova, Olga; Rusyn, Andrii; Shevnya, Sergii; Shparyk, Yaroslav; Sinielnikov, Ivan; Andrusenko, Orest; Trukhyn, Dmytro; Ursol, Grygoriy; Vynnychenko, Ihor; Nguyen, Tien Quang; Pham, Xuan Dung; Castro, Gilberto; Kubota, Kaoru.

In: The Lancet, Vol. 393, No. 10183, 04.05.2019, p. 1819-1830.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042)

T2 - a randomised, open-label, controlled, phase 3 trial

AU - Mok, Tony S.K.

AU - Wu, Yi Long

AU - Kudaba, Iveta

AU - Kowalski, Dariusz M.

AU - Cho, Byoung Chul

AU - Turna, Hande Z.

AU - Castro, Gilberto

AU - Srimuninnimit, Vichien

AU - Laktionov, Konstantin K.

AU - Bondarenko, Igor

AU - Kubota, Kaoru

AU - Lubiniecki, Gregory M.

AU - Zhang, Jin

AU - Kush, Debra

AU - Lopes, Gilberto

AU - Gomez Aubin, Gonzalo

AU - Fein, Luis

AU - Kaen, Diego

AU - Kowalyszyn, Ruben

AU - Lerzo, Guillermo

AU - Martinengo, Gaston

AU - Molina, Matias

AU - Richardet, Eduardo

AU - Picon, Pablo

AU - Varela, Mirta

AU - Zarba, Juan Jose

AU - de Azevedo, Sergio Jobim

AU - Barrios, Carlos Henrique

AU - Beato, Carlos

AU - Cerny, Carlos Alexandre Sydow

AU - De Marchi, Pedro Rafael Martins

AU - Fernandes, Gustavo

AU - Franke, Fabio Andre

AU - Freitas, Helano

AU - Girotto, Gustavo

AU - Lopes, Valeria

AU - Santos, Lucas

AU - Costa, Marcos Andre

AU - Shimada, Andrea Kazumi

AU - Smaletz, Oren

AU - Soares, Joao Paulo Holanda

AU - Victorino, Ana Paula

AU - Ferreira, Carlos

AU - Koleva, Marchela

AU - Koynov, Krassimir

AU - Micheva, Rumyana

AU - Deliverski, Tsvetan

AU - Milanova, Zhasmina

AU - Doganov, Boyan

AU - Cheng, Susanna

AU - De Angelis, Flavia

AU - Speranza, Giovanna

AU - Juergens, Rosalyn Anne

AU - Ksienski, Doran

AU - Fenton, David

AU - Aren, Osvaldo

AU - Caglevic, Christian

AU - Galindo, Hector

AU - Rey, Felipe

AU - Chang, Jianhua

AU - Chen, Gongyan

AU - Chen, Xi

AU - Ouyang, Xuenong

AU - Cheng, Ying

AU - Ding, Zhenyu

AU - Hou, Mei

AU - Fan, Yun

AU - Feng, Jifeng

AU - He, Jianxing

AU - He, Yong

AU - Hu, Yi

AU - Li, Wei

AU - Liu, Xiaoqing

AU - Liu, Zhe

AU - Lu, Shun

AU - Qin, Shukui

AU - Tang, Qiyou

AU - Wang, Buhai

AU - Wang, Kai

AU - Zhang, Li

AU - Zhang, Xin

AU - Zhao, Jun

AU - Wang, Jie

AU - Zhou, Caicun

AU - Zhou, Jianying

AU - Zhou, Qing

AU - Wu, Yilong

AU - Cardona, Andres

AU - Duarte, Ricardo

AU - Gomez Wolff, Luis

AU - Zambrano, Angela

AU - Vallejo, Marcela

AU - Havel, Libor

AU - Kolek, Vitezslav

AU - Kolman, Petr

AU - Koubkova, Leona

AU - Petruzelka, Lubos

AU - Popelkova, Patrice

AU - Roubec, Jaromir

AU - Vanasek, Jaroslav

AU - Vlasek, Tomas

AU - Jaal, Jana

AU - Kuusk, Gerli

AU - Avendano, Oscar

AU - Castro, Hugo

AU - Lopez, Karla

AU - Sandoval, Mario

AU - Ho, Chung Man James

AU - Lo, Sing Hung

AU - Laczo, Ibolya

AU - Piko, Bela

AU - Ostoros, Gyula

AU - Aoe, Keisuke

AU - Fujisaka, Yasuhito

AU - Hirashima, Tomonori

AU - Horiike, Atsushi

AU - Hosomi, Yukio

AU - Hotta, Katsuyuki

AU - Ichiki, Masao

AU - Imamura, Fumio

AU - Iwamoto, Yasuo

AU - Kasahara, Kazuo

AU - Katakami, Nobuyuki

AU - Kato, Terufumi

AU - Murakami, Shuji

AU - Kawaguchi, Tomoya

AU - Kishi, Kazuma

AU - Kubota, Kaoru

AU - Kurata, Takayasu

AU - Torii, Yoshitaro

AU - Nakahara, Yasuharu

AU - Nishimura, Takashi

AU - Ohira, Tatsuo

AU - Saka, Hideo

AU - Sawa, Toshiyuki

AU - Seki, Nobuhiko

AU - Sugawara, Shunichi

AU - Takahashi, Kazuhisa

AU - Takigawa, Nagio

AU - Tanaka, Hiroshi

AU - Yamada, Kazuhiko

AU - Yokoyama, Takuma

AU - Yokoyama, Toshihide

AU - Yoshioka, Hiroshige

AU - Kudaba, Iveta

AU - Purkalne, Gunta

AU - Stara, Zinaida

AU - Cesas, Alvydas

AU - Cicenas, Saulius

AU - Zemaitis, Marius

AU - How, Soon Hin

AU - Liam, Chong Kin

AU - Ong, Choo Khoon

AU - Tho, Lye Mun

AU - Arrieta Rodriguez, Oscar

AU - de The Bustamante Valles, Flor

AU - Hernandez Hernandez, Carlos

AU - Mas, Luis

AU - Vera, Luis

AU - Salas, Jorge

AU - Tejada, Hermes

AU - Edusma-Dy, Regina

AU - Galvez, Christina

AU - Ladrera, Guia Elena Imelda

AU - Tan Chun Bing, Jerry

AU - Jassem, Jacek

AU - Kalinka-Warzocha, Ewa

AU - Karaszewska, Boguslawa

AU - Kazarnowicz, Andrzej

AU - Kowalski, Dariusz

AU - Lesniewski Kmak, Krzysztof

AU - Ramlau, Rodryg

AU - Araujo, Antonio

AU - Barata, Fernando

AU - Gil, Nuno

AU - Hespanhol, Venceslau

AU - Alexandru, Aurelia

AU - Dediu, Mircea

AU - Cherciu, Nelly

AU - Ciurescu, Daniel

AU - Ganea, Doina

AU - Miron, Lucian

AU - Sirbu, Daniela

AU - Turdean, Maria

AU - Emelyanov, Sergey

AU - Karaseva, Nina

AU - Kuzina, Lyudmila

AU - Lazarev, Sergey

AU - Lifirenko, Igor

AU - Bolotina, Larisa

AU - Lipatov, Oleg

AU - Ovchinnikova, Elena

AU - Matrosova, Marina

AU - Alyasova, Anna

AU - Poltoratsky, Artem

AU - Taranov, Pavel

AU - Zarubenkov, Oleg

AU - Cohen, Graham

AU - Dreosti, Lydia

AU - Seolwane, Freddy

AU - Hall, Jacqueline

AU - Hart, Gregory

AU - Jordaan, Christa

AU - Buddu, Sayeuri

AU - Botha, Michiel

AU - Landers, Gregory

AU - Rappaport, Bernardo

AU - Ruff, Paul

AU - Shepherd, Lucinda

AU - Szpak, Waldemar

AU - Ahn, Myung Ju

AU - Cho, Byoung Chul

AU - Kim, Joo Hang

AU - Bergstrom, Per

AU - Ohman, Ronny

AU - Griph, Hakan

AU - Betticher, Daniel

AU - Ochsenbein, Adrian

AU - Zippelius, Alfred

AU - Chan, Gee Chen

AU - Chiu, Chao Hua

AU - Hsia, Te Chun

AU - Su, Wu Chou

AU - Yang, Chih Hsin

AU - Ativitavas, Touch

AU - Danchaivijitr, Pongwut

AU - Srimuninnimit, Vichien

AU - Seetalarom, Kasan

AU - Sookprasert, Aumkhae

AU - Sriuranpong, Virote

AU - Altundag, Ozden

AU - Cay Senler, Filiz

AU - Erman, Mustafa

AU - Goksel, Tuncay

AU - Goker, Erdem

AU - Ozyilkan, Ozgur

AU - Seker, Mesut

AU - Gumus, Mahmut

AU - Turna, Hande

AU - Yumuk, Fulden

AU - Adamchuk, Grigory

AU - Bondarenko, Igor

AU - Ivashchuk, Oleksandr

AU - Ponomarova, Olga

AU - Rusyn, Andrii

AU - Shevnya, Sergii

AU - Shparyk, Yaroslav

AU - Sinielnikov, Ivan

AU - Andrusenko, Orest

AU - Trukhyn, Dmytro

AU - Ursol, Grygoriy

AU - Vynnychenko, Ihor

AU - Nguyen, Tien Quang

AU - Pham, Xuan Dung

AU - Castro, Gilberto

AU - Kubota, Kaoru

PY - 2019/5/4

Y1 - 2019/5/4

N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme.

AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Merck Sharp & Dohme.

UR - http://www.scopus.com/inward/record.url?scp=85064607320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064607320&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(18)32409-7

DO - 10.1016/S0140-6736(18)32409-7

M3 - Article

C2 - 30955977

AN - SCOPUS:85064607320

VL - 393

SP - 1819

EP - 1830

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10183

ER -