Froedtert and the Medical College of Wisconsin, Milwaukee, WI
William Hampton Bradley , Monica Prasad Hayes , Nicolas Taylor , Janet Sue Rader , Erin Bishop , Elizabeth Hopp , Lindsey Allison McAlarnen , Melodee Liegl , Pippa Simpson , Denise Uyar
Background: Patients with metastatic recurrent endometrial cancer have limited effective therapies. Single agent pembrolizumab is utilized in mismatch repair deficient (MMRd) patients, while the combination of lenvatinib and pembrolizumab is now more commonly used in MMR intact patients who have progressed after chemotherapy combinations. This trial investigated a novel three drug regimen. Methods: Patients with recurrent endometrial cancer not amenable to curative intent surgery or radiation after one or two lines of therapy were eligible regardless of histology. This study is a multicenter, open-label, nonrandomized phase II trial. All subjects initially received the three-drug combination of rucaparib, bevacizumab, and atezolizumab. The primary goal of this trial was to estimate the overall response rate in these patients, and secondarily to estimate the progression-free and overall survival of patients treated with this triplet combination. Total enrollment was 30, with the first six subjects participated in a safety lead-in. Treatments until progression, toxicity, or clinician choice. Subjects could continue past progression if, in the estimate of the treating clinician and subject, clinical benefit was being provided. Subjects were eligible for analysis if they received at least one cycle and had one post-dose tumor assessment. The ORR assumption was 27% with a lower bound of 14%. Results: 30 subjects were enrolled between 07/2019 and 06/2021. Of these 26 were evaluable. Median follow up at cut off was 14.9 months. 23 subjects had clinical benefit, with 1 (4%) with CR, 9 (39%) with PR, and 13 (57%) with stable disease as best response. Overall median event-free (progression or death) was 5.3 (95% CI 2.7-7.9) months and overall survival 13.3 (95% CI NA) months at cut off. Median duration of therapy was 4.4 months (IQR 1.7-7.3), with 4 subjects remaining on study directed therapy at data cut off. Histology distribution was 50% serous, 20% endometrioid, and 13% carcinosarcoma. 19 pts were White, 8 African American, 2 identified as Asian, 1 unknown. In the MMR deficient patients, event-free probability was 11.9 months. Grade 3 or 4 treatment related adverse events occurred in 50% patients. Conclusions: To our knowledge, this trial represents the first use of a non-chemotherapy-based triplet therapy for recurrent endometrial cancer. The combination of rucaparib, bevacizumab, and atezolizumab may safely be used to treat recurrent/persistent endometrial cancer. This combination demonstrates clinically meaningful improvement in response, with acceptable toxicity. Enhanced response to therapy was seen in MMR deficient subjects. Clinical trial information: NCT03694262.
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