Effectiveness, toxicity and treatment adjustments of lenvatinib plus pembrolizumab in advanced renal cell carcinoma: a multicenter real-world analysis.

Background: Combinations of checkpoint inhibitors and tyrosine kinase inhibitors are contemporary standards of care in first-line treatment of patients with advanced renal cell carcinoma. Real-world evidence remains scarce. Patients and methods: We retrospectively investigated the tolerability and effectiveness of lenvatinib plus pembrolizumab-approved based on the results of the CLEAR trial-under real-world conditions in 145 patients. Results: The median age was 63 years (range 21-87 years). The majority of patients were male (69%) and had a predominant clear-cell histology (88%). Adverse events (AEs) occurred in 94% of patients, with fatigue (50%), hypertension (39%) and diarrhea (38%) as most common AEs. Grade ≥3 AEs were seen in 59%. Interruption of at least one of the drugs due to toxicities was required in 68% of patients. The dose of lenvatinib was reduced in 56%. The objective response rate was 66%, with 8% of patients achieving a complete remission. Primary progression was seen in 8% of patients. At a median follow-up time of 12.2 months [95% confidence interval (CI) 10.3-15.5 months], 35% of patients experienced disease progression. Progression-free survival at 6 months was 76% (95% CI 71.9% to 79.7%). Twenty-one percent of patients died, most of them due to progressive disease. Limitations of our analysis are the short follow-up period and the retrospective nature of the analyses. Conclusions: Our cohort supports the use of lenvatinib plus pembrolizumab in a real-world population, including CLEAR-ineligible patients. However, AEs should be closely monitored and treatment should be adapted accordingly.