The toxicity observed with full doses of lenvatinib and the underrepresentation of Black participants in the KEYNOTE-775 trial prompted researchers to examine dose reductions, discontinuations, and responses with pembrolizumab plus lenvatinib in patients with uterine cancer. The single-center trial enrolled 12 patients (58.3% Black), and the response rate was 50%, compared with 38% in the KEYNOTE-775 trial.

Positive Results With Decreased Pembrolizumab Plus Lenvatinib Dose

Median progression-free survival was 12 months, with three participants achieving a progression-free survival that was not reached because of ongoing, prolonged responses (>12 months). The rate of dose reductions was 100%, with all but one patient beginning with a decreased dose (median starting dose, 12 mg; range, 10-20 mg). Half of patients with carcinosarcoma (2/4) achieved a partial durable response (50%, including 10 months and not reached). Most of the responders (83%; 5/6) were patients receiving therapy as the second-line or third-line treatment, and one additional patient had stable disease of 11 months that was not included in the response rate. Adverse event rates were 58% for grades 1-2 and 50% for grades 3-4, which were lower than those seen in KEYNOTE-775. Investigators reported notable weight loss, with a median weight loss of 9 kg for all participants and 14 kg for patients responding to treatment. Almost all patients (11/12) began treatment with a decreased dose of 10 mg or 14 mg followed by an attempt at dose escalation among those experiencing little to no adverse events. The researchers also noted that two patients had to suspend treatment with lenvatinib because of grade 3 diarrhea and biopsy-confirmed cardiotoxicity at 13 months and 2.5 months into treatment, respectively. These patients maintained a response to single-agent pembrolizumab, however, with a progression-free survival that had not been reached as of September 24, 2021.

Further Support for KEYNOTE-775

The trial showed that lower-dose lenvatinib plus pembrolizumab continued to demonstrate a notable response rate, with less toxicity than that seen in KEYNOTE-775. These results included high responses rates among Black participants and those with carcinosarcoma, the researchers noted, and the ongoing response to single-agent pembrolizumab. While the study team noted that weight loss should be evaluated in the context of a continuing clinical benefit, they reported that the results further highlight the results from KEYNOTE-775 and the role of this therapy early for patients with recurrent or refractory uterine cancer while also considering a decreased dose for better tolerability and a sustained clinical benefit.