In a phase II trial reported in JAMA Oncology, Konstantinopoulos et al found that the combination of talazoparib and avelumab was active in patients with recurrent mismatch repair–proficient endometrial cancer.
In the U.S. multicenter study, 35 evaluable women with measurable disease, unlimited prior therapies, and any endometrial cancer histology were enrolled between February 2019 and December 2019. Treatment consisted of talazoparib at 1 mg daily and avelumab at 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The co–primary endpoints were objective response and 6-month progression-free survival. The combination was to be considered worthy of further investigation if objective response was achieved in at least four patients or if at least eight patients survived progression-free at 6 months.
Objective responses (all partial) were observed in four patients (11.4%, 95% confidence interval [CI] = 3.2%–26.7%). An additional 20 patients (57.1%) had stable disease of any duration (median duration = 3.8 months; range = 1.7–12.8 months). A total of eight patients (22.9%, 95% CI = 10.4%–40.1%) survived progression-free at 6 months. Overall, clinical benefit (objective response and/or 6-month progression-free survival) was observed in nine patients (25.7%). At a median follow-up of 12.9 months, median progression-free survival was 3.6 months (95% CI = 2.4–5.4 months).
Clinical benefit was observed in 5 (83.3%) of 6 patients with homologous recombination repair (HRR)-altered tumors vs 4 (17.4%) of 23 without HRR-altered tumors (P = .01). Progression-free survival was also improved among patients with HRR-altered tumors (median = 9.1 months vs 3.3 months, P = .03). No associations of clinical benefit with tumor mutational burden, tumor-infiltrating lymphocytes, or PD-L1 status were observed.
The most common treatment-related grade 3 or 4 adverse events were anemia (46%), thrombocytopenia (29%), and neutropenia (11%). Serious adverse events occurred in nine patients (25.7%); the most common were decreased platelet count in three patients and small intestinal obstruction in three, with none of these considered related to treatment. Adverse events led to dose reductions in 17% of patients; no treatment discontinuations due to adverse events were observed. No treatment-related deaths occurred.
The investigators concluded: “The results of this nonrandomized controlled trial suggest that treatment with avelumab and talazoparib demonstrated a favorable toxic effect profile and met the predetermined criteria to be considered worthy of further evaluation in [mismatch repair–proficient endometrial cancer]. Immunogenomic profiling provided insights that may inform ongoing and future studies of polyadenosine diphosphate-ribose polymerase and PD-L1 inhibitor combinations in endometrial cancer.”
Panagiotis A. Konstantinopoulos, MD, PhD, Division of Gynecologic Oncology, Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Pfizer, as part of an alliance between Pfizer and Merck KGaA. For full disclosures of the study authors, visit jamanetwork.org.
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