Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

作者：Thomas Powles, Piotr Tomczak, Se Hoon Park, Balaji Venugopal, Thomas Ferguson, Stefan N. Symeonides, Jaroslav Hájek, Howard Gurney, Yen‐Hwa Chang, Jae‐Lyun Lee, Naveed Sarwar, Antoine Thiery-Vuillemin, Marine Gross‐Goupil, Mauricio Mahave, Naomi B. Haas, Piotr Sawrycki, Joseph E. Burgents, Lei Xu, Kentaro Imai, David I. Quinn, Toni K. Choueiri, Piotr Tomczak, Toni K. Choueiri, Se Hoon Park, Balaji Venugopal, Thomas Ferguson, Jaroslav Hájek, Tzu-Ping Lin, Stefan N. Symeonides, Jae‐Lyun Lee, Piotr Sawrycki, Naomi B. Haas, Howard Gurney, Mauricio Mahave, Naveed Sarwar, Antoine Thiery-Vuillemin, Marine Gross‐Goupil, Christine Chevreau, John M. Burke, Gurjyot K. Doshi, Bohuslav Melichar, Delphine Topart, Stéphane Oudard, Evgeniy Kopyltsov, H. Hammers, David I. Quinn, Ajjai Alva, Juliana de Menezes, Adriano Gonçalves e Silva, Eric Winquist, Alketa Hamzaj, Giuseppe Procopio, Boguslawa Karaszewska, Ewa M. Nowakowska-Zajdel, B. Yа. Alekseev, Rustem Gafanov, А. А. Измайлов, Andrey Semenov, S. G. Afanasyev, Oleg Lipatov, T.B. Powles, Sandy Srinivas, David F. McDermott, Samith T. Kochuparambil, Ian D. Davis, Katriina Peltola, Roberto Sabbatini, Jinsoo Chung, М. I. Shkolnik, В. Б. Матвеев, P. Gajate Borau, Steven McCune, Thomas E. Hutson, Alejandro Dri, Silvio Correia Sales, Carrie Yeung, Carmen Marcela Alcala Castro, Peter J. Boström, Brigitte Laguerre, Consuelo Buttigliero, Ugo De Giorgi, Eugeniy A. Fomin, Yousef Zakharia, Clara Hwang, Eric A. Singer, Jeffrey T. Yorio, David Waterhouse, Rubén Dario Kowalyszyn, Margarita Sonia Alfie, Eduardo Yañez Ruiz, Tomáš Büchler, Krista Kankaanranta, G. Ferretti, Go Kimura, Kazuo Nishimura, Naoya Masumori, Satoshi Tamada, Haruaki Kato, Hiroshi Kitamura, Iwona Danielewicz, Joanna Wojcik-Tomaszewska, Nuria Sala Gonzalez, Kun‐Yuan Chiu, Michael B. Atkins, Elisabeth I. Heath, Gustavo Adolfo Rojas-Uribe, Manuel Enrique Gonzalez Fernandez, Susan Feyerabend, Sandro Pignata, Kazuyuki Numakura, Bozena Cybulska Stopa, Р. А. Зуков, Miguel Á. Climent Durán, Pablo Jose Maroto Rey, Á. Montesa Pino, Chao‐Hsiang Chang, Salil Vengalil, Tom Waddell, Patrick Cobb, Ralph J. Hauke, D. Mark Anderson, John Sarantopoulos, Theodore Stewart Gourdin, Tian Zhang, Gautam Jayram, Luis Fein, Carole A. Harris, Patricia Medeiros Milhomem Beato, Francisco Flores, Angela Estay, Juan Andres Rubiano, Jens Bedke, Stefan Hauser, Andreas Neisius, Jonas Busch, Satoshi Anai, Hiroyuki Tsunemori, Dariusz Sawka, Bożena Sikora-Kupis, José Ángel Arranz, Ignacio Delgado, Chung‐Hsin Chen, Elizabeth A. Gunderson, Scott S. Tykodi, Alan J. Koletsky, Kevin Chen, Manish Agrawal, Diego Kaen, Juan Pablo Sade, Marcelo Tatangelo, Francis Parnis, Fernando Maciel Barbosa, Genevieve Faucher, Nayyer Iqbal, Danièle Marceau, Jean-Benoit Paradis, Nawar Hanna, Alejandro Acevedo, Carolina Ibáñez, Luis J. Villanueva-Rivera, Pedro Pablo Galaz, Isabel Cristina Durango, Ray Manneh, Zdeněk Král, Petra Holečková, Heikki Hakkarainen, Hanna Ronkainen, Sophie Abadie‐Lacourtoisie, Sophie Tartas, Peter J. Goebell, Marc‐Oliver Grimm, Thomas Hoefner, Manfred P. Wirth, Andrej Panic, Wolfgang Schultze-Seemann, Akira Yokomizo, Ryuichi Mizuno, Hirotsugu Uemura, Masatoshi Eto, Masao Tsujihata, Yoshihisa Matsukawa, Yoji Murakami, Miso Kim, Paul Hamberg, Malgorzata Marczewska-Skrodzka, Szczylik Cezary, Alison C. Humphreys, Peter Jiang, Birendra Kumar, Gary Lu, Arpita Desai, José A. Karam, George P. Keogh, Mark T. Fleming, Juan José Zarbá, Viviana E. Leiva, Guillermo Ariel Mendez, S.J. Harris, Stephen J. Brown, João Neif Antonio, Rita de Cássia Costamilan, Roberto Odebrecht Rocha, David Queiroz Borges Muniz, Leandro Brust, Aly‐Khan A. Lalani, Jeffrey Graham, Michael A. Levesque, Francesco Orlandi, Rostislav Kotasek, Jean L. Deville, Delphine Borchiellini, Axel S. Merseburger, Michael Rink, Frederik C. Roos, Ray McDermott, Masafumi Oyama, Yoshiaki Yamamoto, Yoshihiko Tomita, Yuji Miura, Naomasa Ioritani, Hans M. Westgeest, Tomasz Kubiatowski, Wiesław Bal, Regina Gironés Sarrió, Julie Rowe, Debra M. Prow, Francis M. Senecal, Neda Hashemi‐Sadraei, Scott Cole, Stephan D. Kendall, Donald Richards, Ian D. Schnadig, Mukul Kumar Gupta · 发表于：The Lancet Oncology · 年份：2022 · DOI：10.1016/s1470-2045(22)00487-9 · 被引用次数：288 · 研究领域：Renal cell carcinoma treatment、Cancer Research and Treatments、Cancer Immunotherapy and Biomarkers

BACKGROUND: The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. METHODS: In the multicentre, randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial, adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence were enrolled at 213 hospitals and cancer centres in North America, South America, Europe, Asia, and Australia. Eligible participants had an Eastern Cooperative Oncology Group performance status of 0 or 1, had undergone nephrectomy 12 weeks or less before randomisation, and had not received previous systemic therapy for advanced renal cell carcinoma. Participants were randomly assigned (1:1) via central permuted block randomisation (block size of four) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. Randomisation was stratified by metastatic disease status (M0 vs M1), and the M0 group was further stratified by ECOG performance status and geographical region. All participants and investigators involved in study treatment administration were masked to the treatment group as...