Adjuvant therapy with atezolizumab (Tecentriq) did not meet the primary end point of disease-free survival (DFS) in patients with muscle-invasive urothelial cancer (MIUC) at high risk for recurrence versus observation alone in the primary analysis of the IMvigor010 trial.
At a median follow-up of 21.9 months, the rate of DFS was identical in both arms of the trial: 52%. Median DFS was 19.4 months with atezolizumab versus 16.6 months with observation alone. The results were reported at the ASCO 2020 virtual annual meeting.
“The difference in median disease-free survival did not translate to a significant hazard ratio,” said lead investigator Maha H.A. Hussain, MD, FACP, FASCO, Deputy Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
“IMvigor010 was a completely negative trial. No disease-free survival benefit was found for adjuvant atezolizumab,” said discussant of this trial, Toni K. Choueiri, MD, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA. “Adjuvant single-agent atezolizumab is not advised in unselected MIUC, despite there being more than 50% of high-risk patients in this trial.”
Experts expressed disappointment at the result, noting that checkpoint inhibitor therapy does have benefit in the setting of metastatic urothelial carcinoma, but no good explanation for this difference was proposed.
IMvigor010 enrolled 809 patients with MIUC who were at high risk for disease recurrence after primary resection with radical cystectomy or nephroureterectomy with lymph node dissection at least 14 weeks before study randomization. No postsurgical adjuvant radiation or chemotherapy was allowed. Patients who did not receive neoadjuvant chemotherapy were either ineligible for or declined cisplatin therapy.
Patients were randomized in a 1:1 ratio to adjuvant atezolizumab 1200 mg once every 3 weeks for a maximum of 16 cycles or 1 year of observation every 3 weeks. At 18 months, DFS rate was 51% for atezolizumab and 49% for observation, and PD-L1 expression status had no effect on DFS.
Subgroup analysis did not show any trend favoring atezolizumab over observation, regardless of disease stage, receipt of neoadjuvant chemotherapy, nodal status, and geographic site. The overall survival data are not yet mature, and further follow-up is needed.
The safety profile of atezolizumab was similar to what had been reported in advanced urothelial cancer. Adverse events of any cause were reported in 94% of the atezolizumab group and 79% of the placebo group. Grades 1 and 2 adverse events of special interest occurred more often with atezolizumab and were mainly pruritus, fatigue, diarrhea, and rash.
Serious events (31% vs 18%, respectively) and grade 3 or 4 events of any cause were also more common with atezolizumab (37% vs 20%, respectively).
The rate of adverse events leading to discontinuation of atezolizumab (mostly skin and gastrointestinal events) was 16%. Dose interruptions were needed in 33% of patients. “The rate of treatment discontinuations due to adverse events was higher than in other studies of atezolizumab in this setting,” Dr Hussain said.