Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study
Authors: Motzer Robert J. , Porta Camillo , Eto Masatoshi , Powles Thomas , Grünwald Viktor , Hutson Thomas E. , Alekseev Boris , Rha Sun Young , Merchan Jaime , Goh Jeffrey C. , Lalani Aly-Khan A. , De Giorgi Ugo , Melichar Bohuslav , Hong Sung-Hoo , Gurney Howard , Méndez-Vidal María José , Kopyltsov Evgeny , Tjulandin Sergei , Gordoa Teresa Alonso , Kozlov Vadim , Alyasova Anna , Winquist Eric , Maroto Pablo , Kim Miso , Peer Avivit , Procopio Giuseppe , Takagi Toshio , Wong Shirley , Bedke Jens , Schmidinger Manuela , Rodriguez-Lopez Karla , Burgents Joseph , He Cixin , Okpara Chinyere E. , McKenzie Jodi , Choueiri Toni K. ,   for the CLEAR Trial Investigators, Motzer Robert J. , Choueiri Toni , Hutson Thomas , Nordquist Luke , Spigel David , Merchan Jaime , George Saby , Srinivas Sandhya , Curti Brendan , Pippas Andrew , Heath Elisabeth , Rao Subramanya , Gourdin Theodore , Hashmi Mehmood , Burhani Nafisa , Molina Ana , Koletsky Alan , Alter Robert , Alemany Carlos , Gartrell Benjamin , Cusnir Mike , Vyas Harsha , Graff Stephanie , Squillante Christian , Knapp Mark , Percent Ivor , Patel Vijay , Spitz Daniel , Harkness Cameron , Matrana Marc , Overton Lindsay , Richey Stephen , Richards Donald , Ghaddar Habib , Galamaga Robert , Hauke Ralph , Haggerty Joseph , Harris Ronald , Johns Mark , Kochuparambil Samith , Kollmannsberger Christian , Shayegan Bobby , Canil Christina , Winquist Eric , Sperlich Catherine , Bjarnason Georg , Basappa Naveen , Loidl Wolfgang , Horninger Wolfgang , Schmidinger Manuela , D'Hondt Lionel , Schrijvers Dirk , Rutten Annemie , Schatteman Peter , Wynendaele Wim , Luyten Daisy , Sideris Spyridon , Gennigens Christine , Melichar Bohuslav , Katolicka Jana , Tomasek Jiri , Prausova Jana , Buchler Tomas , Holeckova Petra , Barthelemy Philippe , Tosi Diego , Abbar Baptiste , Negrier Sylvie , Oudard Stephane , Voog Eric , Zanetta Sylvie , Rolland Frederic , Bedke Jens , Siemer Stefan , Wirth Manfred , Schleicher Jan , De Santis Maria , Bergmann Lothar , Staehler Michael , Ivanyi Philipp , Lutz Christoph , Von Amsberg Gunhild , Boegemann Martin , Zimmermann Uwe , McDermott Raymond , Bambury Richard , Donnellan Paul , Breathnach Oscar , Leibowitz-Amit Raya , Goldman Olesya , Peer Avivit , Sarid David , Nechushtan Hovav , Berger Raanan , Neiman Victoria , Calabro Fabio , Pedrazzoli Paolo , Boccardo Francesco , Hamzaj Alketa , Riccardi Ferdinando , De Giorgi Ugo , Pignata Sandro , Santarossa Sandra , Massari Francesco , Tonini Giuseppe , Accettura Caterina , Carrozza Francesco , Sabbatini Roberto , Verzoni Elena , Biscaldi Elisa , Suelmann Britt , van den Eertwegh Alfonsus , van Thienen Hans , Kalinka Ewa , Jassem Jacek , Sulzyc-Bielicka Violetta , Mandziuk Slawomir , Tjulandin Sergei , Karyakin Oleg , Alyasova Anna , Alekseev Boris , Zyrianov Alexander , Matveev Vsevolod , Kopyltsov Evgeny , Kozlov Vadim , Arranz Arija Jose Angel , Garcia Pablo Borrega , Climent Duran Miguel Angel , Valderrama Begona Perez , Gonzalez Emilio Esteban , Garcia del Muro Solans Francisco Javier , Garcia-Donas Jimenez Jesus , Gordoa Teresa Alonso , Maroto Rey Jose Pablo , Gonzalez Begoña Mellado , Mendez Vidal Maria Jose , Vazquez Javier Puente , Rodriguez Cristina Suarez , Pulido Enrique Grande , Crespo Guillermo , Nuñez Natalia Fernandez , Martinez Ignacio Duran , Beyer Joerg , Fischer Natalie , Glen Hilary , Frazer Ricky , Allison Jennifer , Powles Thomas , Malik Jahangeer , Ralph Christy , Rudman Sarah , Geldart Thomas , Bamias Aristotelis , Baka Sofia , Georgoulias Vassilios , Papazisis Konstantinos , Kalofonos Haralabos , Timotheadou Eleni , Byun Seok-Soo , Lim Bumjin , Rha Sun Young , Seo Seong Il , Chung Jinsoo , Kim Miso , Hong Sung-Hoo , Lee Jae Lyun , Park Se Hoon , Kwon Tae Gyun , Davis Ian , Wong Shirley , Byard Ian , Weickhardt Andrew , Gurney Howard , Goh Jeffrey , Osawa Takahiro , Masumori Naoya , Hatakeyama Shingo , Saito Mitsuru , Tomita Yoshihiko , Miura Yuji , Nagata Masayoshi , Kimura Go , Oya Mototsugu , Takagi Toshio , Nakamura Yu , Hasumi Hisashi , Iwamura Masatsugu , Komiya Akira , Komaru Atsushi , Oyama Masafumi , Matsukawa Yoshihisa , Soga Norihito , Kato Minoru , Nozawa Masahiro , Miyake Makito , Nakano Yuzo , Edamura Kohei , Hinata Nobuyuki , Okazoe Homare , Takahashi Masayuki , Eto Masatoshi , Oba Kojiro , Kishida Takeshi , Ukimura Osamu 
Published: January 2024

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.