Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer

Objective. We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/ lenvatinib in recurrent endometrial cancer ina real-world clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes. Methods. Retrospectively, we reviewed toxicity, treatment responses, and survival outcomes of patients with recurrent endometrial cancer who received >= 1 cycle of pembrolizumab/lenvatinib. We compared subgroups based on lenvatinib starting dose (recommended [20 mg] vs reduced [<20 mg]) and histologic type. Results. We analyzed 70 patients (recommended dose cohort, n = 16; reduced dose cohort, n = 54). The most common starting dose was 14 mg daily. Compared to the reduced dose cohort, the recommended dose co-hort had a significantly higher mean number of lenvatinib dose reductions due to side effects (1.1 vs. 0.4; p = 0.003) and significantly shorter median time to treatment toxicity (1.3 vs. 3.7 days; p = 0.0001). Response rates did not differ significantly between the recommended and reduced dose cohorts (28.6% vs. 38.3%, respec-tively; p = 0.752). Two patients, both in the reduced dose cohort, had complete responses. Patients with carci-nosarcoma histology had response and clinical benefit rates of 25% (3 of 12) and 58.3% (7 of 12), respectively. There were no differences between the 2 dose cohorts with respect to progression-free (p = 0.245) or overall survival (p = 0.858). Conclusion. In clinical practice, a lower starting dose of lenvatinib (14 mg daily) in combination with pembrolizumab was safe and efficacious in recurrent endometrial cancer. The combination produced responses in endometrial carcinosarcomas. Larger studies are required to validate these findings. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

In recurrent endometrial cancer patients, pembrolizumab/lenvatinib combination therapy with a lower starting dose of lenvatinib (14 mg daily) was found to be safe and effective. There were no significant differences in response rates, survival outcomes, and toxicity between the recommended dose group and reduced dose group. However, the recommended dose group required more lenvatinib dose reductions and experienced quicker onset of treatment toxicity.