Results from a study presented at the virtual 2021 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer support a lower starting dose of lenvatinib in clinical practice than what is currently recommended by the FDA.

“Pembrolizumab/lenvatinib demonstrated impressive response rates in advanced/recurrent endometrial cancer in a recent phase 2 clinical trial, leading to its accelerated FDA approval. However, tolerability of the recommended 20 mg starting dose of lenvatinib may pose clinical challenges,” explained Jeffrey How, MD, MPH, MD Anderson Cancer Center, Houston, TX, and colleagues.

This study evaluated the use of pembrolizumab and lenvatinib for endometrial carcinoma in clinical practice using preliminary efficacy and toxicity data at the University of Texas MD Anderson Cancer Center.

Patients with recurrent or advanced endometrial cancer who received ≥1 cycle of pembrolizumab/lenvatinib treatment were included in the study. Toxicity was evaluated through rates of hospitalization, treatment interruptions or discontinuations, and dose reductions. Efficacy was evaluated by best radiologic response to treatment and clinical benefit was defined as having stable disease or partial/complete response.

A total of 67 patients were included in the analysis. Median follow-up was 5 months and the median number of prior lines of therapy was 2. Histologic subtypes included endometrioid (n = 19), serous (n = 19), carcinosarcoma (n = 13), mixed (n = 8), clear cell (n = 4), and other (n = 4).

The most common starting dose of lenvatinib was 14 mg (n = 43; 64.2%), followed by 20 mg (n = 15; 22.4%). Treatment-related hospitalization occurred in 26.9% of patients but did not differ between the lenvatinib dosage groups. Patients who received the 20 mg doing of lenvatinib had significantly higher treatment discontinuations and dose reductions vs those who received the lower starting dose. In addition, patients who received the higher starting dose had a trend toward higher treatment interruptions compared with those who had the lower starting dose.

Among 56 patients with evaluable radiologic response, 21 (37.5%) had either a partial (n = 18) or complete response (n = 3), and 18 patients (32.1%) had stable disease. All patients with a complete response had a starting lenvatinib dose of 14 mg. No differences in response to therapy were noted for lenvatinib 20 mg dosing (23.1%) vs <20 mg (41.9%; P = .56) or clinical benefit rates (53.8% vs 74.4%, P = .18; respectively).

In addition, no differences in response rates were reported among histologic subtypes (P = 0.76). Patients with carcinosarcoma histology had a response rate of 25% and clinical benefit rate of 58.3%.

“In treatment of recurrent/advanced endometrial cancer, lower starting dosage of lenvatinib was associated with fewer treatment interruptions/discontinuations and dose de-escalations compared to the FDA recommended 20 mg dosage level while maintaining equivalent response and clinical benefit rates. Furthermore, patients with carcinosarcoma histology also appeared to benefit from pembrolizumab/lenvatinib,” Dr How and colleagues concluded.

“While larger studies are needed to validate these safety and efficacy findings, our preliminary data supports starting a lower dosage of lenvatinib in clinical practice,” they added.—Janelle Bradley

How J, et al. The use of pembrolizumab and lenvatinib combination therapy in endometrial cancer: An examination of toxicity and treatment efficacy in clinical practice. Presented at: the virtual 2021 SGO Annual Meeting on Women’s Cancer; March 19-25, 2021. Abstract 10775.