A large phase I trial offers further evidence that the anti–programmed death ligand 1 (PD-L1) agent avelumab is generally well tolerated and results in relatively few serious adverse events. The trial covered a number of malignancies, including urothelial carcinoma.
The US Food and Drug Administration granted accelerated approval to avelumab (Bavencio) in May 2017, for the treatment of locally advanced or metastatic urothelial carcinoma patients whose disease progressed on or following platinum-containing chemotherapy. The new analysis, led by Karen Kelly, MD, of the University of California-Davis Comprehensive Cancer Center in Sacramento, aimed to further characterize the safety profile of this agent.
The investigators pooled the safety data from the phase I JAVELIN Solid Tumor trial, which included 1,650 patients, and the phase II JAVELIN Merkel trial (88 patients); the agent was also approved in early 2017 for the treatment of metastatic Merkel cell carcinoma. All 1,738 patients received avelumab at a dose of 10 mg/kg every 2 weeks. The results were published in Cancer.
The most common malignancies included in the trials were non–small-cell lung cancer (340 patients), gastric and gastroesophageal cancer (252 patients), urothelial carcinoma (249 patients), and ovarian cancer (228 patients), with fewer numbers of other solid tumors. About half of the patients (53.5%) were under 65 years old, and about half were male (51.7%).
Almost all patients experienced any-grade all-causality adverse events (97.6%), and 58.0% had grade 3 or higher events. Treatment-related adverse events (TRAEs) occurred in 67.0% of the cohort, and grade 3 TRAEs were seen in 10.2%.
The most common TRAEs of any grade included fatigue in 17.7% of patients and infusion-related reactions in 17.0% of patients. Grade 3 or higher fatigue occurred in 1.0% of patients, as did grade 3 or higher increased lipase; no other grade 3 or higher TRAE occurred in more than 0.6% of patients.
A total of 107 patients (6.2%) had TRAEs that led to permanent discontinuation of avelumab; the most common of these was infusion-related reactions in 1.8%. Serious TRAEs occurred in 6.2% of patients, again with infusion-related reactions as the most common (0.9%).
About half of the cohort had died at the time of the analysis (52.4%), with disease progression representing the most common cause of death (42.8%). Fifty-nine patients (3.4%) died because of an adverse event that was unrelated to the treatment, and the primary cause of death was unknown or missing in 6.0% of the cohort. A total of four deaths were determined to be primarily caused by a TRAE.
“Avelumab generally was well tolerated and had a manageable safety profile in a large population of patients with advanced solid tumors,” the authors concluded. “This analysis of a large population of patients across a broad scope of tumor types suggests that avelumab was associated with an incidence of immune-related adverse events that is consistent with that of other immune checkpoint inhibitors.”