Lenvatinib Plus Pembrolizumab Provides Durable Benefits in Advanced RCC

Updated results from the CLEAR trial suggest that lenvatinib and pembrolizumab can provide durable benefits over sunitinib in patients with treatment-naïve, advanced renal cell carcinoma (RCC).

Researchers found that, with a median follow-up of 4 years, overall survival (OS) was improved with lenvatinib and pembrolizumab. Progression-free survival (PFS) was improved with the combination as well. These and other updates from the trial were reported in the Journal of Clinical Oncology.

The phase 3 CLEAR trial (ClinicalTrials.gov Identifier: NCT02811861) enrolled patients with previously untreated, advanced RCC. They were randomly assigned to receive lenvatinib and pembrolizumab (n=355) or sunitinib alone (n=357). Baseline characteristics were generally well balanced between the arms.

Pembrolizumab was given at 200 mg once every 3 weeks for up to 35 cycles. Lenvatinib was given at 20 mg daily until discontinuation. Sunitinib was given at 50 mg daily, 4 weeks on and 2 weeks off, until discontinuation. Patients continued on treatment until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

The median follow-up for OS was 49.8 months in the lenvatinib-pembrolizumab arm and 49.4 months in the sunitinib arm. At the data cutoff, 58 patients in the lenvatinib-pembrolizumab arm and 24 patients in the sunitinib arm remained on study treatment.

The median OS was 53.7 months in the lenvatinib-pembrolizumab arm and 54.3 months in the sunitinib arm (hazard ratio [HR], 0.79; 95% CI, 0.63-0.99; P =.0424). The 36-month OS rate was 66.4% and 60.2%, respectively. The patients who completed all 35 cycles of pembrolizumab and continued on lenvatinib monotherapy had a 36-month OS rate of 94.2%.

“[W]ith a median OS follow-up time of about 4 years, lenvatinib plus pembrolizumab continued to show clinically meaningful efficacy compared with sunitinib as a first-line treatment for aRCC,” the researchers wrote.

The proportion of patients who received subsequent anticancer therapy was 51.0% in the lenvatinib-pembrolizumab arm and 68.9% in the sunitinib arm. When the researchers attempted to adjust for the impact of subsequent anticancer therapies, OS remained superior for patients who received lenvatinib and pembrolizumab (HR, 0.55; 95% CI, 0.44-0.69).

The median follow-up for PFS was 39.2 months with lenvatinib-pembrolizumab and 20.6 months with sunitinib. The median PFS was 23.9 months with lenvatinib-pembrolizumab and 9.2 months with sunitinib (HR, 0.47; 95% CI, 0.38-0.57; P <.0001).

The median second PFS was 43.3 months with lenvatinib-pembrolizumab and 25.9 months with sunitinib (HR, 0.63; 95% CI, 0.51-0.77).

“Safety results were consistent with those from the primary analysis and with the established safety profiles of each monotherapy and of the combination in patients with other solid tumors,” the researchers wrote.

The rate of treatment-emergent adverse events (TEAEs) was 99.7% in the lenvatinib-pembrolizumab arm and 98.5% in the sunitinib arm. The rate of grade 3 or higher TEAEs was 84.9% and 74.7%, respectively. There were 16 fatal TEAEs in the lenvatinib-pembrolizumab arm and 12 in the sunitinib arm.

The most common TEAEs of any grade (in the lenvatinib-pembrolizumab arm and sunitinib arm, respectively) were diarrhea (64.2% and 50.9%), hypertension (57.4% and 42.9%), hypothyroidism (50.0% and 27.4%), and fatigue (42.9% and 37.6%).

“[L]envatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naive patients with aRCC,” the researchers concluded.

Disclosures: This research was supported by Eisai Inc and Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor