Low-dose lenvatinib and anti-programmed cell death protein-1 combination therapy in patients with heavily pre-treated recurrent ovarian and endometrial cancer: a pilot study

Objective Treatment options for heavily pre-treated recurrent ovarian and endometrial cancer are limited. Lenvatinib plus anti-programmed cell death protein-1 (PD-1) combination therapy has been efficacious in advanced endometrial cancer, but at the recommended dose level, high-grade adverse events occur and lead to drug discontinuation. This study evaluated the feasibility of low-dose lenvatinib plus anti-PD-1 therapy in patients with recurrent ovarian and endometrial cancer. Methods This is a single-arm, protocol-based pilot study. Patients with recurrent ovarian cancer or endometrial cancer who had at least one line of previous therapy were included and given lenvatinib 8 or 12 mg daily (based on the patient’s weight) and anti-PD-1 therapy. The primary endpoint was the objective response rate. Results Twenty-one patients were enrolled, including 15 with ovarian cancer and six with endometrial cancer. All patients were pre-treated, and the median number of lines of previous treatment of the ovarian and endometrial cancer cohorts was three and two, respectively. After a median follow-up of 11.0 months (range 6.8–23.9), the objective response rate for the ovarian cancer and endometrial cancer cohorts was 46.7% (95% CI 21.3% to 73.4%) and 66.7% (95% CI 22.3% to 95.7%), respectively. The median duration of response for the ovarian cancer and endometrial cancer cohorts was 5.3 (95% CI 0 to 11.7) and 6.1 (95% CI 2.4 to 9.8) months, respectively. The median progression-free survival for the ovarian cancer and endometrial cancer cohorts was 4.1 (95% CI 2.6 to 5.6) and 6.6 (95% CI 1.7 to 11.5) months, respectively. No grade 4 or 5 adverse events occurred. Eight (38.1%) patients had a lenvatinib dose reduction. There was no discontinuation of lenvatinib alone, and only one patient discontinued both drugs due to adverse events. Conclusion Low-dose lenvatinib in combination with anti-PD-1 therapy showed promising efficacy and favorable tolerability in patients with heavily pre-treated ovarian and endometrial cancer.