A Single-arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients with Advanced Non-Clear Cell Renal
Thomas E Hutson1, M Dror Michaelson2, Timothy M Kuzel3
1Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.
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.
Clinical Registration:
This trial is registered at ClinicalTrials.Gov as NCT02915783.
Insights
Lenvatinib plus everolimus showed promising efficacy for advanced non-clear cell renal cell carcinoma (nccRCC) with a 26% objective response rate. This combination therapy demonstrated manageable side effects in patients receiving first-line treatment.
Area of Science:
- Oncology
- Medical research
- Clinical trials
Background:
- Non-clear cell renal cell carcinoma (nccRCC) comprises a small percentage of renal cell carcinoma cases.
- Lenvatinib (tyrosine kinase inhibitor) combined with everolimus (mTOR inhibitor) is approved for advanced RCC post-antiangiogenic therapy.
Purpose of the Study:
- To evaluate the safety and efficacy of lenvatinib plus everolimus as a first-line treatment for advanced nccRCC.
- To assess the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in this patient population.
Main Methods:
- An open-label, single-arm, phase 2, multicenter study.
- Enrolled 31 patients with unresectable advanced or metastatic nccRCC without prior anticancer therapy.
- Administered lenvatinib (18 mg) plus everolimus (5 mg) orally once daily.
Main Results:
- The overall objective response rate (ORR) was 26% (95% CI 12-45), with partial responses observed in 8 patients.
- Median progression-free survival (PFS) was 9.2 months (95% CI 5.5-NE).
- Median overall survival (OS) was 15.6 months (95% CI 9.2-NE).
- Common adverse events included fatigue (71%), diarrhea (58%), and decreased appetite (55%).
Conclusions:
- Lenvatinib plus everolimus demonstrated promising anticancer activity as a first-line treatment for advanced nccRCC.
- The safety profile was consistent with known side effects of the drug combination.
- Further investigation is warranted due to the observed efficacy and manageable safety profile.
More Related Videos
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Related Concept Videos
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:06Renal Drug Clearance: Overview
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...
02:56Treatment Resistant Cancers
01:15Renal Drug Excretion: Overview
A nephron consists of two primary structures: the renal corpuscle and the renal tubule. The renal corpuscle contains the glomerulus, a network of capillaries where the first step of renal excretion, glomerular filtration, occurs. Blood pressure forces water, ions, and small molecules...