In a phase II trial reported in the Journal of Clinical Oncology, Panagiotis A. Konstantinopoulos, MD, PhD, and colleagues found that letrozole plus abemaciclib produced activity in patients with estrogen receptor (ER)-positive recurrent endometrial cancer.

Panagiotis A. Konstantinopoulos, MD, PhD

Study Details

In the study, 30 patients enrolled from three U.S. sites between September 2019 and August 2021 received letrozole at 2.5 mg once daily and abemaciclib at 150 mg twice daily. Among the 30 patients, 29 had received prior chemotherapy (median number of prior lines of therapy = 3) and 15 had received prior hormonal therapy; 28 had endometrioid histology.

The primary endpoints were objective response rate on Response Evaluation Criteria in Solid Tumors version 1.1 and progression-free survival at 6 months.

Efficacy Outcomes

Objective responses (all partial) were observed in nine patients (30%, 95% confidence interval [CI] = 14.7%–49.4%); all responses occurred among patients with endometrioid adenocarcinomas. Responses were observed regardless of tumor grade, prior hormonal therapy (responses in 4 of 15 patients with prior therapy and in 5 of 15 without), mismatch repair status, and progesterone receptor status. An additional 13 patients (43%) had stable disease. Median duration of response was 7.4 months (95% CI = 3 months to not evaluable).  

Median progression-free survival was 9.1 months (95% CI = 3.5–16.5 months), with a 6-month rate of 55.6% (95% CI = 35.1%–72%). As noted by the investigators, these findings met the predetermined criteria for worthiness of the regimen for further evaluation of four or more objective responses and eight or more patients with progression-free survival at 6 months.

An exploratory tumor profiling analysis suggested a number of mechanistically relevant candidates for predictors of response (CTNNB1, KRAS, and CDKN2A mutations) or absence of response (TP53 mutations; response in 1 of 11 patients with a TP53 mutation and in 6 of 11 with wild-type TP53); the findings require independent validation.

Adverse Events

The most common grade ≥ 3 treatment-related adverse events were neutropenia (20%) and anemia (17%), followed by diarrhea, thrombocytopenia, and increased alanine aminotransferase levels (7% each, all grade 3). Diarrhea of any grade was observed in 21 patients (70%; grade 1 or 2 in 19 patients). Reversible increases in creatinine levels (all grade 1 or 2) were observed in 10 patients (33%). Treatment was discontinued due to adverse events in two patients (7%). No treatment-related deaths were observed.

The investigators concluded: “Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER-positive endometrioid endometrial cancer.”

Dr. Konstantinopoulos, of the Gynecologic Oncology Program, Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

Disclosure: The investigator-initiated study was funded by Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.org.