New Combination Could Prove Beneficial After Immunotherapy in Patients with Clear Cell RCC

The combination of Lenvima (lenvatinib) plus everolimus was found to be safe and effective in patients with clear cell renal cell carcinoma (RCC) who have previously received immune checkpoint inhibitors in prior lines of therapy, according to the findings of an exploratory analysis of a phase 2 trial, which were presented virtually at the 2021 ASCO Genitourinary Cancers Symposium.

“Because of changes to the treatment landscape, first-line treatment often includes immune checkpoint inhibitor (ICI) therapy, and therefore, it is important to examine the antitumor response and safety of lenvatinib [plus] everolimus in this patient subgroup,” the study investigators, who were led by Sumanta K. Pal, MD, wrote in their presentation.

Because Lenvima is already approved for use in combination with everolimus for the treatment of patients with RCC following prior VEGF-inhibitor therapy, based on results of a previous phase 1/2 study, investigators set out to evaluate the combination of Lenvima at two different starting doses plus a set dose of everolimus in patients who had prior VEGF inhibitor therapy.

A total of 343 patients were enrolled in the trial, of which, 90 received ICIs in a prior line of therapy. These patients received 14 mg (n = 49) or 18 mg (n = 41) of daily lenvatinib plus 5 mg of daily everolimus. If they experienced no intolerable adverse events (AEs) or dose reductions at 4 weeks, patients in the 14 mg starting dose group were escalated to 18 mg.

The trial’s primary endpoints were the objective response rate (ORR) at week 24 and the rate of grade 2 or higher AEs. Secondary endpoints included progression-free survival (PFS), ORR, and overall survival (OS).

The median PFS in patients receiving prior ICI therapy was 12.0 months in the 14 mg group and 12.9 months in the 18 mg group. Median OS was 17.1 months with the 14 mg starting dose of lenvatinib and 18.0 months with 18 mg lenvatinib.

The ORRs were higher for patients who received 18 mg lenvatinib at 51.3%, compared to 30.2% for those in the 14 mg lenvatinib group.

The safety profile for the subset of patients with prior ICI experience was similar to the overall patient population. In the 14 mg and 18 mg groups, the most common any-grade treatment-emergent AEs included (61.2% vs 70.7%, respectively) decreased appetite (44.9% vs 51.2%), stomatitis (30.6% vs 43.9%), nausea (32.7% vs 43.9%), hypertension (42.9% vs 39.0%), fatigue (34.7% vs 34.1%), asthenia (30.6% vs 29.3%), vomiting (32.7% vs 51.2%), and proteinuria (32.7% vs 43.9%).

The investigators concluded by stating that, “when taken together, the efficacy results by investigator [assessment] and IIR are supportive of the higher lenvatinib 18 mg starting dose compared with 14 mg.”

A version of this story originally appeared on Cancer Network as “Lenvatinib/Everolimus Combo May Be Acceptable After Immunotherapy in Clear Cell RCC”

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