TY - JOUR
T1 - Lenvatinib plus pembrolizumab versus sunitinib in first-line treatment of advanced renal cell carcinoma
T2 - final prespecified overall survival analysis of CLEAR, a phase III study
AU - Motzer, Robert J.
AU - Porta, Camillo
AU - Eto, Masatoshi
AU - Powles, Thomas
AU - Grünwald, Viktor
AU - Hutson, Thomas E.
AU - Alekseev, Boris
AU - Rha, Sun Young
AU - Merchan, Jaime
AU - Goh, Jeffrey C.
AU - Lalani, Aly Khan A.
AU - De Giorgi, Ugo
AU - Melichar, Bohuslav
AU - Hong, Sung Hoo
AU - Gurney, Howard
AU - Mendez Vidal, Maria Jose
AU - Kopyltsov, Evgeny
AU - Tjulandin, Sergei
AU - Gordoa, Teresa Alonso
AU - Kozlov, Vadim
AU - Alyasova, Anna
AU - Winquist, Eric
AU - Maroto, Pablo
AU - Kim, Miso
AU - Peer, Avivit
AU - Procopio, Giuseppe
AU - Takagi, Toshio
AU - Wong, Shirley
AU - Bedke, Jens
AU - Schmidinger, Manuela
AU - Rodriguez-Lopez, Karla
AU - Burgents, Joseph
AU - He, Cixin
AU - Okpara, Chinyere E.
AU - McKenzie, Jodi
AU - Choueiri, Toni
AU - The CLEAR Trial Investigators
AU - Nordquist, Luke
AU - Spigel, David
AU - George, Saby
AU - Srinivas, Sandhya
AU - Curti, Brendan
AU - Pippas, Andrew
AU - Heath, Elisabeth
AU - Rao, Subramanya
AU - Gourdin, Theodore
AU - Hashmi, Mehmood
AU - Burhani, Nafisa
AU - Molina, Ana
AU - Koletsky, Alan
AU - Alter, Robert
AU - Alemany, Carlos
AU - Gartrell, Benjamin
AU - Cusnir, Mike
AU - Vyas, Harsha
AU - Graff, Stephanie
AU - Squillante, Christian
AU - Knapp, Mark
AU - Percent, Ivor
AU - Patel, Vijay
AU - Spitz, Daniel
AU - Harkness, Cameron
AU - Matrana, Marc
AU - Overton, Lindsay
AU - Richey, Stephen
AU - Richards, Donald
AU - Ghaddar, Habib
AU - Galamaga, Robert
AU - Hauke, Ralph
AU - Haggerty, Joseph
AU - Harris, Ronald
AU - Johns, Mark
AU - Kochuparambil, Samith
AU - Kollmannsberger, Christian
AU - Shayegan, Bobby
AU - Canil, Christina
AU - Sperlich, Catherine
AU - Bjarnason, Georg
AU - Basappa, Naveen
AU - Loidl, Wolfgang
AU - Horninger, Wolfgang
AU - D'Hondt, Lionel
AU - Schrijvers, Dirk
AU - Rutten, Annemie
AU - Schatteman, Peter
AU - Wynendaele, Wim
AU - Luyten, Daisy
AU - Sideris, Spyridon
AU - Gennigens, Christine
AU - Katolicka, Jana
AU - Tomasek, Jiri
AU - Prausova, Jana
AU - Buchler, Tomas
AU - Holeckova, Petra
AU - Barthelemy, Philippe
AU - Tosi, Diego
AU - Abbar, Baptiste
AU - Negrier, Sylvie
AU - Oudard, Stephane
AU - Voog, Eric
AU - Zanetta, Sylvie
AU - Rolland, Frederic
AU - Siemer, Stefan
AU - Wirth, Manfred
AU - Schleicher, Jan
AU - De Santis, Maria
AU - Bergmann, Lothar
AU - Staehler, Michael
AU - Ivanyi, Philipp
AU - Lutz, Christoph
AU - Von Amsberg, Gunhild
AU - Boegemann, Martin
AU - Zimmermann, Uwe
AU - McDermott, Raymond
AU - Bambury, Richard
AU - Donnellan, Paul
AU - Breathnach, Oscar
AU - Leibowitz-Amit, Raya
AU - Goldman, Olesya
AU - Sarid, David
AU - Nechushtan, Hovav
AU - Berger, Raanan
AU - Neiman, Victoria
AU - Calabro, Fabio
AU - Pedrazzoli, Paolo
AU - Boccardo, Francesco
AU - Hamzaj, Alketa
AU - Riccardi, Ferdinando
AU - Pignata, Sandro
AU - Santarossa, Sandra
AU - Massari, Francesco
AU - Tonini, Giuseppe
AU - Accettura, Caterina
AU - Carrozza, Francesco
AU - Sabbatini, Roberto
AU - Verzoni, Elena
AU - Biscaldi, Elisa
AU - Suelmann, Britt
AU - Van Den Eertwegh, Alfonsus
AU - Van Thienen, Hans
AU - Kalinka, Ewa
AU - Jassem, Jacek
AU - Sulzyc-Bielicka, Violetta
AU - Mandziuk, Slawomir
AU - Karyakin, Oleg
AU - Zyrianov, Alexander
AU - Matveev, Vsevolod
AU - Arranz Arija, Jose Angel
AU - Garcia, Pablo Borrega
AU - Climent Duran, Miguel Angel
AU - Valderrama, Begona Perez
AU - Gonzalez, Emilio Esteban
AU - Garcia Del Muro Solans, Francisco Javier
AU - Garcia-Donas Jimenez, Jesus
AU - Gonzalez, Begoña Mellado
AU - Vazquez, Javier Puente
AU - Rodriguez, Cristina Suarez
AU - Pulido, Enrique Grande
AU - Crespo, Guillermo
AU - Nuñez, Natalia Fernandez
AU - Martinez, Ignacio Duran
AU - Beyer, Joerg
AU - Fischer, Natalie
AU - Glen, Hilary
AU - Frazer, Ricky
AU - Allison, Jennifer
AU - Malik, Jahangeer
AU - Ralph, Christy
AU - Rudman, Sarah
AU - Geldart, Thomas
AU - Bamias, Aristotelis
AU - Baka, Sofia
AU - Georgoulias, Vassilios
AU - Papazisis, Konstantinos
AU - Kalofonos, Haralabos
AU - Timotheadou, Eleni
AU - Byun, Seok Soo
AU - Lim, Bumjin
AU - Seo, Seong Il
AU - Chung, Jinsoo
AU - Lee, Jae Lyun
AU - Park, Se Hoon
AU - Kwon, Tae Gyun
AU - Davis, Ian
AU - Byard, Ian
AU - Weickhardt, Andrew
AU - Osawa, Takahiro
AU - Masumori, Naoya
AU - Hatakeyama, Shingo
AU - Saito, Mitsuru
AU - Tomita, Yoshihiko
AU - Miura, Yuji
AU - Nagata, Masayoshi
AU - Kimura, Go
AU - Oya, Mototsugu
AU - Nakamura, Yu
AU - Hasumi, Hisashi
AU - Iwamura, Masatsugu
AU - Komiya, Akira
AU - Komaru, Atsushi
AU - Oyama, Masafumi
AU - Matsukawa, Yoshihisa
AU - Soga, Norihito
AU - Kato, Minoru
AU - Nozawa, Masahiro
AU - Miyake, Makito
AU - Nakano, Yuzo
AU - Edamura, Kohei
AU - Hinata, Nobuyuki
AU - Okazoe, Homare
AU - Takahashi, Masayuki
AU - Oba, Kojiro
AU - Kishida, Takeshi
N1 - Copyright the American Society of Clinical Oncology 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2024/4/10
Y1 - 2024/4/10
N2 - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.
AB - Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.
UR - http://www.scopus.com/inward/record.url?scp=85189700658&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.01569
DO - 10.1200/JCO.23.01569
M3 - Article
C2 - 38227898
AN - SCOPUS:85189700658
SN - 0732-183X
VL - 42
SP - 1222
EP - 1228
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -