As reported in The Lancet Oncology by Joaquim Bellmunt, MD, PhD, and colleagues, the phase III IMvigor010 trial showed no improvement in disease-free survival with adjuvant atezolizumab vs observation in patients with muscle-invasive urothelial carcinoma.

Study Details

In the open-label trial, 809 patients from sites in 24 countries were randomly assigned between October 2015 and July 2018 to receive atezolizumab at 1,200 mg every 3 weeks for 16 cycles or up to 1 year (n = 406) or observation (n = 403). Patients were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. They had ypT2–4a or ypN+ tumors following neoadjuvant chemotherapy or pT3–4a or pN+ tumors if no neoadjuvant chemotherapy had been given.

Patients who did not receive neoadjuvant chemotherapy had to have been ineligible for or declined cisplatin-based adjuvant chemotherapy. Patients could not have received postsurgical radiotherapy or previous adjuvant chemotherapy.

Joaquim Bellmunt, MD, PhD

The primary endpoint was disease-free survival in the intention-to-treat population.

Disease-Free Survival

Median follow-up was 21.9 months (interquartile range = 13.2–29.8 months). Median disease-free survival was 19.4 months (95% confidence interval [CI] = 15.9­–24.8 months) in the atezolizumab group vs 16.6 months (95% CI = 11.2–24.8 months) in the observation group (stratified hazard ratio = 0.89, 95% CI = 0.74–1.08, P = .24), with 18-month rates of 51% vs 49%. Results of subgroup analyses were similar to the primary analysis, with no benefit of atezolizumab being observed according to PD-L1 status.

At interim analysis of overall survival, death had occurred in 29% vs 31% of patients. Formal analysis was not performed due to hierarchical testing. Overall survival at 12 and 18 months was 88% vs 81% and 79% vs 73%. Subsequent anticancer therapy was received by 31% vs 34% of patients, including chemotherapy in 27% vs 25%, immunotherapy in 9% vs 21%, and targeted therapy in 5% vs 2%.

Adverse Events

Adverse events of any grade occurred in 94% of patients in the atezolizumab group and 79% of patients in the observation group. The most common grade 3 to 4 adverse events were urinary tract infection (8% vs 5%), pyelonephritis (3% vs 4%), and anemia (2% vs 2%). Treatment-related grade 3 to 4 adverse events occurred in 16% of the atezolizumab group, with the most common being arthralgia (n = 5), colitis (n = 4), and increased alanine aminotransferase (n = 4).

Serious adverse events occurred in 31% vs 18% of patients. Adverse events led to discontinuation of treatment in 16% of the atezolizumab group. A fatal treatment-related adverse event (acute respiratory distress syndrome) occurred in one patient in the atezolizumab group.

The investigators concluded, “To our knowledge, IMvigor010 is the largest, first-completed phase III adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time.”

Dr. Bellmunt, of Beth Israel Deaconess Medical Center, Harvard Medical School, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit thelancet.com.