Seeking to improve oncologic outcomes in patients with metastatic urothelial carcinoma (UC), Rohan Garje, MD, and colleagues theorized that the combination of avelumab and docetaxel could “enhance cancer cell death by releasing neoantigens and potentiating anti-tumor immune-mediated cytotoxicity,” without sacrificing safety. Presenting in Poster Session B, Urothelial Carcinoma, at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Dr. Garje reported that avelumab plus docetaxel was safe and demonstrated “promising efficacy” for patients with platinum-refractory or -ineligible metastatic UC.
The two-part trial enrolled 21 patients with locally advanced or metastatic UC that had progressed during or following platinum-based chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. In phase one, the docetaxel dose for phase two was determined with a 3+3 design. In part two, standard avelumab dose (10mg/kg) and the recommended phase two docetaxel dose was administered every three weeks over six cycles. Following that, avelumab was continued every two weeks. The primary endpoint was safety, while secondary efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
According to the report, only one of the six patients treated at the highest docetaxel dose in part one, 75 mg/m2, experienced dose-limiting toxicity, and the dosage was judged safe for the dose expansion cohort. Fifteen additional patients were recruited for the dose expansion cohort for a total of 20 evaluable patients. The study’s authors observed a ORR in 70% of participants (complete response: 30%, partial response: 40%, stable disease: 5%, progressive disease: 25%). The median PFS was 9.2 months (range: 1.5–25.8 months), while the median OS was not reached. Finally, the most common grade III or IV adverse events were febrile neutropenia, transaminitis, diarrhea, anemia, and neutropenia.
Noting the strong OS and zero reported treatment-related deaths, Dr. Garje and colleagues judged the docetaxel and avelumab combination therapy to be safe. They felt that the clinical outcomes observed were favorable enough to warrant “further studying in patients with platinum-refractory or ineligible metastatic urothelial cancer.”