Journal
EUROPEAN UROLOGY
Volume 80, Issue 2, Pages 162-170Publisher
ELSEVIER
DOI: 10.1016/j.eururo.2021.03.015
Keywords
Non-clear cell renal cell carcinoma; Chromophobe; Papillary; Everolimus; First-line treatment; Lenvatinib
Categories
Funding
- Eisai Inc., Woodcliff Lake, NJ, USA
- Merck Sharp & Dohme Corp., Kenilworth, NJ, USA
- Eisai Inc.
- Merck Sharp & Dohme Corp, Kenilworth, NJ, USA
Ask authors/readers for more resources
The combination of lenvatinib plus everolimus as a first-line treatment showed promising anticancer activity for patients with advanced non-clear cell renal cell carcinoma, with a relatively high objective response rate and manageable treatment-related adverse events.
Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for <= 20% of RCC cases. Lenvatinib (a multitargeted tyrosine kinase inhibitor) in combination with everolimus (an mTOR inhibitor) is approved for the treatment of advanced RCC after one prior antiangiogenic therapy. Objective: To determine the safety and efficacy of lenvatinib plus everolimus as a first-line treatment for patients with advanced nccRCC. Design, setting, and participants: This open-label, single-arm, multicenter, phase 2 study enrolled patients with unresectable advanced or metastatic nccRCC and no prior anticancer therapy for advanced disease. Intervention: Lenvatinib (18 mg) plus everolimus (5 mg) orally once daily. Outcome measurements and statistical analysis: The primary endpoint was the objective response rate (ORR) as assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety assessments. The 95% confidence intervals (CIs) for ORRs were calculated using the two-sided Clopper-Pearson method. Median PFS and median OS were estimated using the Kaplan-Meier product-limit method and their 95% CIs were estimated via a generalized Brookmeyer and Crowley method. Results and limitations: The study (start date: February 20, 2017) enrolled 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2). At the data cutoff date (July 17, 2019), the best overall response was a partial response (eight patients: papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) for an overall ORR of 26% (95% CI 12-45). Median PFS was 9.2 mo (95% CI 5.5-not estimable), and median OS was 15.6 mo (95% CI 9.2-not estimable). The most common treatment-emergent adverse events were fatigue (71%), diarrhea (58%), decreased appetite (55%), nausea (55%), and vomiting (52%). Limitations include the small sample size and single-arm design. Conclusions: Lenvatinib plus everolimus showed promising anticancer activity in patients with advanced nccRCC with an ORR of 26% and is worthy of further study. The safety profile was consistent with the established profile of the study-drug combination. Patient summary: We examined the combination of lenvatinib plus everolimus as the first therapy for 31 patients who had advanced nccRCC. We found that this treatment seemed effective, because most patients had a decrease in tumor size and manageable treatment-related side effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available