THE PHASE 3 CLEAR trial demonstrated a significant improvement in overall survival (OS) with lenvatinib plus pembrolizumab over sunitinib as first-line therapy for advanced renal cell carcinoma (RCC). In a presentation during the 2021 ASCO Genitourinary Cancers Symposium, Dr. Robert J. Motzer (Memorial Sloan Kettering Cancer Center, New York, NY) reported the results of a comparison between two combination therapies including lenvatinib and sunitinib in patients with advanced RCC. The results of the CLEAR trial were published simultaneously in The New England Journal of Medicine.
In the trial, a total of 1069 patients with advanced RCC and no systemic therapy were randomized in a 1:1:1 ratio to the three treatment groups. Median progression-free survival (PFS) was 23.9 months for lenvatinib plus pembrolizumab, 14.7 months for lenvatinib plus everolimus, and 9.2 months for sunitinib (P<0.0001 for each combination vs. sunitinib). While PFS was longer for both combination treatment groups compared with sunitinib, benefit in OS was seen only with lenvatinib plus pembrolizumab (hazard ratio, 0.66; 95% confidence interval, 0.49-0.88; P=0.005) compared with sunitinib. Treat- ment-related grade ³3 adverse events that occurred in 10% of patients were observed in 71.6% of patients who received lenvatinib plus pembrolizumab compared with 58.8% for sunitinib; this difference may have been due to the longer treatment duration with lenvatinib plus pembrolizumab than with sunitinib. Adverse events judged to be related to the trial treatment across treatment groups included diarrhea and hypertension.
It is not known how lenvatinib plus pembrolizumab compares with other recently identified combination therapies involving checkpoint inhibitors in the first-line setting for advanced RCC. However the complete response rate of 16.1% is very noteworthy, suggesting that lenvatinib plus pembrolizumab is a promising addition to the armamentarium of medical oncologists, Dr. Motzer concluded.
Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.
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(6, suppl):68. Abstract 269. doi: 10.1200/JCO.2021.39.6_suppl.269
Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi: 10.1056/NEJMoa2035716