In the final overall survival analysis from the phase III IMvigor130 trial reported in The Lancet Oncology, Aristotelis Bamias, MD, and colleagues found no significant advantage in overall survival with atezolizumab monotherapy vs chemotherapy in untreated patients with locally advanced or metastatic urothelial carcinoma.
Aristotelis Bamias, MD
As stated by the investigators, the primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy vs placebo plus platinum-based chemotherapy. However, no improvement in overall survival benefit on interim analysis was observed for the atezolizumab/chemotherapy group. The current analysis compared the atezolizumab monotherapy group in the trial vs the chemotherapy group.
Study Details
In the global trial, 1,413 patients from sites in 35 countries were randomly assigned 1:1:1 between July 2016 and July 2018 to receive atezolizumab at 1,200 mg every 3 weeks plus platinum-based chemotherapy (n = 451), atezolizumab monotherapy (n = 362), or placebo plus platinum-based chemotherapy (n = 400). For the latter two groups, atezolizumab at 1,200 mg or placebo was administered every 3 weeks. Chemotherapy consisted of 21-day cycles of gemcitabine (1,000 mg/m² on day 1 and day 8 plus investigator’s choice of carboplatin at area under the curve = 4.5 or cisplatin 70 mg/m²).
The overall survival outcomes for the atezolizumab monotherapy group vs the chemotherapy group were not formally statistically evaluated due to hierarchical testing and the failure of atezolizumab/chemotherapy to improve overall survival vs chemotherapy. Outcomes of interest in the current analysis were overall survival among the 360 patients in the atezolizumab group and 359 in the chemotherapy group who were enrolled concurrently (intention-to-treat [ITT] population) and in the population of patients with PD-L1 tumor-infiltrating immune cell expression of IC2/3.
Key Points
At data cutoff at the end of August 2022, median follow-up was 13.4 months (interquartile range = 6.2–30.8 months). Median overall survival was 15.2 months (95% confidence interval [CI] = 13.1–17.7 months) in the atezolizumab monotherapy group vs 13.3 months (95% CI = 11.9–15.6 months) in the chemotherapy group (stratified hazard ratio [HR] = 0.98, 95% CI = 0.82–1.16).
Among patients with high PD-L1 expression (IC2/3), death occurred in 52 (59%) of 88 patients in the atezolizumab group vs 58 (69%) of 85 in the chemotherapy group. Median overall survival was 27.5 months (95% CI = 17.7–49.4 months) in the atezolizumab monotherapy group vs 16.7 months (95% CI = 10.0–26.1 months) in the chemotherapy group (stratified HR = 0.70, 95% CI = 0.48–1.03).
The investigators concluded, “The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals.”
Dr. Bamias, of National and Kapodistrian University of Athens, Greece, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit thelancet.com.
