Robert J. Motzer, MD, on Next Steps for the Phase 3 CLEAR Trial for Advanced RCC

Investigators compared lenvatinib plus either pembrolizumab or everolimus versus sunitinib in patients with advanced renal cell carcinoma in the CLEAR trial.

According to results from the phase 3 CLEAR trial (NCT02811861) presented at the 2021 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, compared with sunitinib (Sutent), combination treatment with lenvatinib (Lenvima) and pembrolizumab (Keytruda) demonstrated significant improvements in progression-free survival (PFS), overall survival, and objective response rate (ORR) among patients with advanced renal cell carcinoma (RCC). In addition, 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 an interview with CancerNetwork®, Robert J. Motzer, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed what he believes these study results will lead to as well as what is planned in other studies going forward.


I think that lenvatinib [plus] pembrolizumab should be considered a standard treatment program. This awaits regulatory review and hopefully approval, but certainly from looking at the data, this is a highly effective [treatment regimen]. Safety is manageable. It’s a very attractive program for first-line therapy for clear cell RCC.

There are some other studies that are moving forward. There’s another combination trial that’s being planned–a large phase 3 trial that’s going to be using lenvatinib [plus] pembrolizumab as the standard arm for other combinations. I see this as setting a new standard and hopefully [it] will also receive regulatory approval and be available for patients outside of studies.


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