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
Robert J. Motzer, Camillo Porta, Masatoshi Eto, Thomas Powles, Viktor Grünwald, Thomas E. Hutson, B. Yа. Alekseev, Sun Young Rha, Jaime R. Merchan, Jeffrey C. Goh, Aly‐Khan A. Lalani, Ugo De Giorgi, Bohuslav Melichar, Sung‐Hoo Hong, Howard Gurney, María José Méndez, Evgeny Kopyltsov, Sergei Tjulandin, Teresa Alonso‐Gordoa, Vadim Kozlov, Anna Alyasova, Eric Winquist, Pablo Maroto, Miso Kim, Avivit Peer, Giuseppe Procopio, Toshio Takagi, Shirley Wong, Jens Bedke, Manuela Schmidinger, Karla Rodriguez-Lopez, Joseph E. Burgents, Cixin He, Chinyere E. Okpara, Jodi A. McKenzie, Toni K. Choueiri, for the CLEAR Trial Investigators, Robert J. Motzer, Toni K. Choueiri, Thomas E. Hutson, Luke T. Nordquist, David R. Spigel, Jaime R. Merchan, Saby George, Sandhya Srinivas, Brendan D. Curti, Andrew Pippas, Elisabeth I. Heath, Subramanya Rao, Theodore Stewart Gourdin, Mehmood Hashmi, Nafisa Burhani, Ana M. Molina, Alan J. Koletsky, Robert Alter, C. Alemany, Benjamin A. Gartrell, Mike Cusnir, Harsha Vyas, Stephanie L. Graff, Christian Squillante, Mark Knapp, Ivor Percent, Vijay Patel, Daniel L. Spitz, C. Harkness, Marc Matrana, Lindsay Overton, Stephen Richey, Donald Richards, Habib M. Ghaddar, Robert Galamaga, Ralph J. Hauke, Joseph Haggerty, Ronald Harris, Mark Johns, Samith T. Kochuparambil, Christian Kollmannsberger, Bobby Shayegan, Christina Canil, Eric Winquist, Catherine Sperlich, Georg A. Bjarnason, Naveen S. Basappa, Wolfgang Loidl, Wolfgang Horninger, Manuela Schmidinger, Lionel D’Hondt, Dirk Schrijvers, Annemie Rutten, Peter Schatteman, Wim Wynendaele, Daisy Luyten, Spyridon Sideris, Christine Gennigens, Bohuslav Melichar, Jana Katolická, Jiří Tomášek, Jana Prausová, Tomáš Büchler
Abstract
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.