In this trial, patients with measurable clear cell RCC (1 prior VEGF-targeted therapy; prior PD-1/PD-L1 therapy permitted) were randomly assigned 1:1 to lenvatinib 14 mg or 18 mg (starting dose) plus everolimus 5 mg daily. The trial schema is as follows:
There were 115 patients in the lenvatinib 14 mg arm that were titrated to lenvatinib 18 mg at cycle 2 as they did not experience intolerable grade 2 or any grade ≥3 treatment-related adverse events requiring dose reduction within cycle 1. This analysis assessed objective response rate and progression-free survival by independent imaging review per RECIST v1.1. Additionally, efficacy endpoints (objective response rate, progression-free survival, and overall survival) were analyzed by investigator assessment per RECIST v1.1 by prior immune checkpoint inhibitor status.
There were 311 patients (lenvatinib 14 mg arm, n=156; lenvatinib 18 mg arm, n=155) included in the efficacy analysis and 341 patients (lenvatinib 14 mg arm, n=173; lenvatinib 18 mg arm, n=168) included in the summary safety analysis. Objective response rate by independent imaging review (lenvatinib 14 mg arm: 39.7%, 95% CI 32.1–47.4; lenvatinib 18 mg arm: 38.7%, 95% CI 31.0–46.4) was similar between treatment arms. Progression free survival by independent imaging review was numerically longer in the lenvatinib 18 mg arm (median 12.9 months, 95% CI 9.2–17.1) versus the lenvatinib 14 mg arm (median 11.0 months, 95% CI 9.3–12.9). In 82 patients with prior immune checkpoint inhibitor therapy, for the lenvatinib 14 mg (n=43) versus 18 mg (n=39) arms (95% CI):
- Objective response rate was 30.2% (17.2–46.1) versus 51.3% (34.8–67.6) by investigator assessment
- Median progression-free survival was 12.0 months (8.9–16.7) versus 12.9 months (8.4–NE) by investigator assessment, HR 1.27, 90% CI 0.74-2.20
- Median overall survival was 17.1 months (10.6–NE) versus 18.0 months (13.1–NE), HR 1.28, 90% CI 0.75-2.18
As previously reported, the safety profile was similar in both treatment arms: 71.7% of patients in the lenvatinib 14 mg arm and 76.8% of patients in the lenvatinib 18 mg arm had grade 3/4 treatment-related adverse events.
Dr. Pal concluded this presentation with the following summary points:
- The objective response rate was similar between treatment arms and progression-free survival was numerically longer in the lenvatinib 18 mg arm per independent imaging review
- Efficacy outcomes were generally numerically improved for the lenvatinib 18 mg arm compared with the lenvatinib 14 mg arm, regardless of prior immune checkpoint inhibitor therapy
- As previously reported, safety was similar in both treatment arms
- These results further support starting patients with RCC at the higher 18 mg dose of lenvatinib plus everolimus 5 mg
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021
- Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomized, phase 2, open-label, multi-centre trial. Lancet Oncol 2015;16(15):1473-1482.