Avelumab and Talazoparib Demonstrate Promising Safety Profile Recurrent pMMR Endometrial Cancer

In a population of patients with recurrent mismatch repair proficient endometrial cancer, treatment with avelumab and talazoparib appeared to be well tolerated.

Treatment with avelumab (Bavencio) and talazoparib (Talzenna) resulted in an acceptable safety profile among patients with recurrent mismatch repair proficient endometrial cancer with efficacy findings meeting criteria for further evaluation, according to results from a phase 2 study (NCT02912572).

The most frequent grade 3/4 treatment-related adverse effects (TRAEs) reported from 35 patients in the safety and efficacy analysis included anemia (46%), thrombocytopenia (29%), and neutropenia (11%). Investigators did not report any cases of treatment discontinuation due to adverse effects. The only grade 4 AE was thrombocytopenia (9%) and no cases of grade 5 TRAEs were reported. Dose reductions were necessary in 17% of patients due to toxicities. In total, 25.7% of patients experienced serious AEs, which included decreased platelet count (n = 3) and small intestinal obstruction (n = 3); neither AE was associated with the study’s regimen.

“Although other studies have reported HRR [homologous recombination repair] alterations in [endometrial cancer], to our knowledge, this is the first study prospectively evaluating a PARP inhibitor–containing regimen specifically in [endometrial cancer] and demonstrating activity in [endometrial cancers] with HRR alterations,” the authors wrote.

Of the patients in the efficacy analysis, 25.7% experienced clinical benefit after achieving a minimum of 1 of 2 primary end points, including an improvement in objective response or progression-free survival at 6 months. The objective response rate (ORR) was 11.4% and included 4 partial responses. Moreover, the 6-month progression-free survival (PFS) rate was 22.9%. With a median follow-up of 12.9 months at the data cut-off in November 2020, the median PFS was 3.6 months (95% CI, 2.4-5.4). In particular, tumors with homologous recombination repair alterations were associated with greater clinical benefit following administration of avelumab and talazoparib. Factors not associated with clinical benefit included tumor mutational burden, tumor-infiltrating lymphocytes, and PD-L1 status.

Patients who enrolled on the study were treated with 10 mg/kg of intravenous avelumab every 2 weeks and 1 mg of continuous talazoparib daily until progression or unacceptable toxicity.The study included a total of 37 patients who enrolled from February 2019 to December 2019. The population had previously received treatment with a carboplatin and paclitaxel chemotherapy regimen.

The trial’s primary end points were PFS at 6 months or longer and ORR by RECIST 1.1 criteria. Secondary end points were PFS and safety.

Additional findings from the study highlighted a stable disease rate of 57.1%, with a median duration of stable disease of 3.8 months. Moreover, 9 patients experienced progressive disease and 2 were unevaluable following discontinuation prior to post-baseline imaging.

Reference

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. Published online July 28, 2022. doi:10.1001/jamaoncol.2022.2181