Talazoparib Plus Avelumab Demonstrates Clinical Benefit for Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer

Talazoparib plus avelumab demonstrated promising clinical benefit in patients with recurrent mismatch repair proficient endometrial cancer that merits further study, according to data from a phase 2 clinical trial.

“Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration–approved immunotherapy for mismatch repair proficient endometrial cancer is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen,” wrote lead author Panagiotis A Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute, Boston, MA, and coauthors, calling attention to, “the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent [mismatch repair proficient endometrial cancer].”

From February 21, 2019 to December 4, 2019, the open-label clinical trial enrolled 35 patients with recurrent mismatch repair proficient endometrial cancer. All patients received 1 mg talazoparib orally once a day and 10 mg/kg intravenous avelumab every 2 weeks. The coprimary objectives of the study were objective response rate (ORR) and rate of progression-free survival (PFS) at 6 months.

Treatment with talazoparib and avelumab met at least 1 of the 2 coprimary end points in 9 (25.7%) trial patients. There were 4 (11.4%) patients who experienced confirmed objective response rates (all partial responses), and 8 (22.9%) who experienced 6-month PFS. Additionally, there was an association found between tumors with homologous recombination repair alterations and clinical benefit from avelumab plus talazoparib. Tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status were not associated with clinical benefit.

Anemia (46% of patients), thrombocytopenia (29%), and neutropenia (11%) were the most common grade 3/4 treatment-related adverse events. There were no discontinuations of therapy due to treatment-related adverse events.

“These study findings suggest that treatment with avelumab and talazoparib has a favorable toxic effects profile and support further investigation in certain subsets of patients with recurrent [mismatch repair proficient endometrial cancer].” concluded Dr Konstantinopoulos and colleagues.

Source:

Konstantinopoulos PA, Gockley AA, Xiong N, et al. Evaluation of treatment with talazoparib and avelumab in patients with recurrent mismatch repair proficient endometrial cancer. JAMA Oncol. 2022;8(9):1317-1322. doi:10.1001/jamaoncol.2022.2181