Adjuvant Atezolizumab Fails to Meet Primary Study Endpoint in High-Risk Bladder Cancer

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Adjuvant atezolizumab, a PD-L1–blocking antibody, failed to meet the primary endpoint of disease-free survival in patients at high risk of recurrence of muscle-invasive bladder cancer compared with observation alone, according to the primary analysis of the IMvigor010 trial reported during the ASCO20 Virtual Scientific Program.1 At a median follow-up of 21.9 months, the rate of disease-free survival was identical in both arms of the trial: 52%. Median disease-free survival was 19.4 months with atezolizumab vs 16.6 months with observation.

“The difference in median disease-free survival did not translate to a significant hazard ratio,” said lead author Maha H.A. Hussain, MD, FACP, FASCO, Deputy Director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University’s Feinberg School of Medicine, Chicago.

Maha H.A. Hussain, MD, FACP, FASCO

Maha H.A. Hussain, MD, FACP, FASCO

Study Details and Key Findings

IMvigor010 enrolled 809 patients at high risk of recurrence after primary resection with radical cystectomy or nephroureterectomy with lymph node dissection at least 14 weeks prior to randomization. No postoperative adjuvant radiation therapy or chemotherapy was allowed. Patients not treated with neoadjuvant chemotherapy had to be either cisplatin-ineligible or have declined cisplatin. All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 as well as available tissue for programmed cell death ligand (PD-L1) testing. Participants were randomly assigned 1:1 to receive adjuvant atezolizumab at 1,200 mg once every 3 weeks for a maximum of 16 cycles or 1 year of observation every 3 weeks.

The rate of 18-month disease-free survival was 51% with atezolizumab and 49% with observation. Disease-free survival was similar regardless of PD-L1 status.

In patients with PD-L1 immunohistochemistry (IC0) 0/1 disease (n = 210 in the atezolizumab group and 207 in the observation group), the rate of disease-free survival was 56% and 58%, respectively. In the PD-L1 IC2/3 subgroup (n = 196 in each arm), the rate of disease-free survival was 48% and 45%, respectively. Subgroup analysis failed to show any trend favoring atezolizumab over observation, including stage, receipt of neoadjuvant chemotherapy, nodal status, and geographic site.

“The difference in median disease-free survival did not translate to a statistically significant hazard ratio.”
— Maha H.A. Hussain, MD, FACP, FASCO

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Median overall survival was not reached in either arm of the trial. Survival data are not yet mature, and follow-up is ongoing.

Safety Profile

The safety profile of atezolizumab was consistent with that observed in other studies of atezolizumab monotherapy in advanced urothelial cancer. Adverse events leading to discontinuation of atezolizumab (mostly skin and gastrointestinal events) were reported in 16% of patients. Dose interruptions were needed in 33%.

“The rate of treatment discontinuations due to adverse events was higher than in other studies of atezolizumab in this setting,” Dr. Hussain noted.

Adverse events of any cause were reported in 94% of the atezolizumab group and 79% of the observation group. Serious adverse events (31% vs 18%, respectively) and grade 3 or 4 adverse events of any cause (37% vs 20%, respectively) were also more common with atezolizumab. As would be expected, grades 1 and 2 adverse events of special interest were more frequently observed with atezolizumab, most commonly rash, hypothyroidism, and hepatitis. 

Publisher's Note: This article was originally published in the July 10, 2020 issue of The ASCO Post.

DISCLOSURE: Dr. Hussain reported financial relationships with Sanofi/Genzyme, Genentech, Genentech/Roche, Aptitude Health, Epics, AstraZeneca, Bayer, Pfizer, and Astellas Pharma, and has served as a consultant for Daiichi Sankyo.


1. Hussain MHA, Powles T, Albers P, et al: IMvigor010: Primary analysis from a phase III randomized study of adjuvant atezolizumab versus observation in high-risk muscle-invasive urothelial carcinoma. ASCO20 Virtual Scientific Program. Abstract 5000.

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