Long-term follow-up of a phase I trial showed that atezolizumab remained well tolerated over more than 3 years, with durable clinical benefit in some patients with heavily pretreated metastatic urothelial carcinoma.
“In phase I and II studies, atezolizumab demonstrated durable objective responses and good tolerability in patients with inoperable locally advanced or metastatic urothelial carcinoma,” wrote study authors led by Daniel P. Petrylak, MD, of Yale Cancer Center in New Haven, Connecticut. The agent is now approved in the United States and Europe for certain urothelial carcinoma patients, but its long-term safety profile has not been previously well characterized.
The new analysis included 95 patients from the expansion cohort of an ongoing phase I trial; they were followed for a median of 37.8 months. Most patients were male (76%), and the median age was 66 years; this was a heavily pretreated population, with 47% receiving atezolizumab as third-line or greater therapy. The results were published in JAMA Oncology.
Patients received atezolizumab for a median of 3 months (range, 0 to 44 months) and a median of 5 doses. A total of 23 patients (24%) were treated for at least 1 year, and 14 patients (15%) continued treatment at the time of data cutoff.
Treatment-related adverse events (TRAEs) of any grade were reported in 64 patients (67%); grade 3/4 TRAEs were seen in 9 patients (9%), and only one of those was a grade 4 event (increased γ-glutamyltransferase level). The most common TRAE of any grade was fatigue (18%), followed by asthenia (14%), decreased appetite (13%), and pruritus (13%). Only asthenia (2 patients) and increased aspartate aminotransferase level (2 patients) occurred at grade 3 in more than a single patient.
“Most TRAEs occurred within the first year of treatment,” the authors wrote. After 63 adverse events were seen in year 1, this declined to 13 in year 2, 7 in year 3, and 1 in year 4. There were no treatment-related serious adverse events beyond year 1.
Twenty-five patients had an objective response, including 9 with a complete response; another 18 patients had stable disease. The median duration of response was 22.1 months, and 10 of the 25 responders (40%) had an ongoing response at the time of data cutoff. The median progression-free survival was 2.7 months, and the median overall survival was 10.1 months.
“Collectively, clinical results reported here compare well with published results for other checkpoint inhibitors or chemotherapy and support a continuing role for atezolizumab in altering treatment paradigms and outcomes in patients with metastatic urothelial carcinoma,” the authors concluded.