The CLEAR trial compared treatment with lenvatinib plus either pembrolizumab or everolimus versus sunitinib in patients with advanced renal cell carcinoma.
Results from the phase 3 CLEAR trial (NCT02811861), presented at the 2021 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, found that compared with sunitinib (Sutent), combination treatment with lenvatinib (Lenvima) and pembrolizumab (Keytruda) demonstrated significant improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) among patients with advanced renal cell carcinoma (RCC). Additionally, combination treatment with lenvatinib plus everolimus (Afinitor) demonstrated significant improvements in PFS and ORR within this patient population.
Importantly, the safety profile of each combination was also found to be manageable and consistent with the known single-agent profiles.
In this study, participants were randomized 1:1:1 to receive either lenvatinib plus pembrolizumab, lenvatinib plus everolimus, or sunitinib. The primary end point was PFS by Independent Review Committee per RECIST v1.1; secondary end points included OS, ORR, and safety.
In an interview with CancerNetwork®, Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, spoke about the results of this study and what the data indicate regarding the best treatment option.
The results of the analysis [were] really striking. The primary end points were progression-free survival for both lenvatinib and pembrolizumab [as well as] lenvatinib and everolimus versus sunitinib, and the trial met the primary endpoint for each of those arms showing a longer progression-free survival compared to sunitinib. There [were also] higher response rates with each of the lenvatinib-containing arms, and particularly striking was the high response rate of 71% with lenavtinib [and] pembrolizumab.
What differentiated the 2 arms in combination with sunitinib was this survival analysis. For lenvatinib [and] pembrolizumab, there was a survival benefit compared to sunitinib; but we didn’t see that survival benefit with lenvatinib [and] everolimus. The response rates were higher with both combinations, but they were the highest with lenvatinib [and pembrolizumab]. Progression-free survival [was also] longer but really the longest with lenvatinib [and pembrolizumab]. The high proportion of complete responses and survival benefit [observed with lenvatinib plus pembrolizumab] make that the preferable choice of treatment in that trial.
Motzer RJ, Porta C, Eto M, et al. Phase 3 trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) monotherapy as a first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) (CLEAR study). J Clin Oncol. 2021;39(suppl 6):269. doi: 10.1200/JCO.2021.39.6_suppl.269