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 - The CLEAR Trial Investigators
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 - Méndez-Vidal, María José
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 K.
AU - Choueiri, Toni
AU - Hutson, Thomas
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 - Kwon, Tae Gyun
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
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 - https://www.scopus.com/pages/publications/85189700658
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 -
SDG 3 Good Health and Well-being