Avelumab and Talazoparib Treatment in Patients with Advanced Urothelial Cancer - Expert Commentary

Talazoparib is a PARP inhibitor used to treat patients with genetic alterations in BRCA1/2 or other genes. PARP inhibitors may exhibit synergy in conjunction with immune checkpoint inhibitors. The JAVELIN PARP Medley trial was initiated to define the safety and efficacy of combination treatment with avelumab and talazoparib in a specific subset of patients.  

The study cohort consisted of 223 patients with solid tumors. The mean age was 63.2 years, and 52.5% of participants were male. Among the twelve patients in phase 1b, nine had metastatic castration-resistant prostate cancer (mCRPC), 2 had triple-negative breast cancer (TNBC), and 1 had ovarian cancer. Dose-limiting toxic effects occurred in 25% of patients. The recommended phase 2 dose for both drugs was determined from this initial phase. Phase 2 consisted of 211 patients. The median duration of treatment was 4.6 months for avelumab and 4.4 months for talazoparib. In patients with urothelial cancer, the overall response rate was 15% (95% CI, 5.7%-29.8%). Interestingly, the response rate was similar in patients with or without prior platinum therapy. The duration of response range was 3.9 to more than 14.7 months, but the median duration of response was not reached. One patient harbored a BRCA alteration and PD-L1 negative status - exhibited a complete response at data cutoff.

The most common treatment-related adverse events (TRAEs) in the study overall were anemia (60.5%), thrombocytopenia (49.3%), and neutropenia (13.9%). Grade 3 or 4 TRAEs that occurred in more than 5% of patients included anemia (33.6%), thrombocytopenia (21.5%), and neutropenia (13.9%). Talazoparib dose was reduced due to effects in 34.5% of patients, while treatment discontinuation occurred in 7.6% of patients. Immune-related events occurred in 13% of patients, of which 3.6% were grade 3 or 4 events. Finally, 21.5% of patients experienced infusion-related reactions.

Overall, there was no significant difference in patient outcomes associated with the addition of talazoparib. The only exception to this finding was patients with TNBC, BRCA-altered ovarian cancer, and HR-positive, ERBB2-negative, and DDR-positive breast cancer. However, it should be noted that the number of patients in the urothelial cancer subgroup was relatively small, warranting a larger study to provide conclusive results on whether this combination treatment may be beneficial.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. Yap TA, Bardia A, Dvorkin M, et al. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial [published online ahead of print, 2022 Nov 17]. JAMA Oncol. 2022;e225228. doi:10.1001/jamaoncol.2022.5228
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