In a final overall survival analysis of the phase III IMvigor130 trial reported in The Lancet Oncology, Enrique Grande, MD, and colleagues found no significant advantage in overall survival with atezolizumab plus chemotherapy vs chemotherapy alone in the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma.
As noted by the investigators, the primary analysis of the trial showed a significant progression-free survival benefit of first-line atezolizumab plus platinum-based chemotherapy vs placebo plus platinum-based chemotherapy in patients with locally advanced or metastatic urothelial carcinoma. No overall survival benefit was observed at interim analyses. The current analysis is the final overall survival analysis for atezolizumab/chemotherapy vs chemotherapy.
Enrique Grande, MD
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 every 3 weeks plus platinum-based chemotherapy (n = 451), atezolizumab monotherapy (n = 362), or placebo plus platinum-based chemotherapy (n = 400). For both groups in the current analysis, chemotherapy consisted of 21-day cycles of gemcitabine at 1,000 mg/m² on day 1 and day 8 plus investigator choice of carboplatin at AUC 4.5 or cisplatin at 70 mg/m².
The co-primary endpoints of the study were investigator-assessed progression-free survival and overall survival for the atezolizumab/chemotherapy group vs the chemotherapy group in the intention-to-treat (ITT) population. The prespecified boundary for significance for the overall survival analysis was one-sided P = .021.
Key Findings
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 16.1 months (95% confidence [CI] = 14.2–18.8 months) in the atezolizumab/chemotherapy group vs 13.4 months (95% CI = 12.0–15.3 months) in the chemotherapy group (stratified hazard ratio = 0.85, 95% CI = 0.73–1.00, one-sided P = 0.23—thus not achieving the criterion for significance).
Overall survival rates at 1, 2, and 3 years were 60% (95% CI = 55%–65%) vs 55% (95% CI = 50%–60%), 38% (95% CI = 33%–42%) vs 32% (95% CI = 28%–37%), and 26% (95% CI = 22%–30%) vs 22% (95% CI = 17%–26%), respectively.
After discontinuing study treatment, 125 patients (28%) in the atezolizumab group and 125 (31%) in the chemotherapy group received nonprotocol chemotherapy; 38 patients (8%) vs 98 patients (25%) received nonprotocol immunotherapy.
Overall, treatment-related deaths occurred in nine patients (2%) in the atezolizumab/chemotherapy group (due to acute kidney injury, dyspnea, hepatic failure, hepatitis, neutropenia, pneumonitis, respiratory failure, sepsis, and thrombocytopenia) and four patients (1%) in the chemotherapy group (due to unexplained death, diarrhea, febrile neutropenia, and toxic hepatitis).
The investigators concluded, “Progression-free survival benefit with first-line combination of atezolizumab plus platinum-based chemotherapy did not translate into a significant improvement in overall survival in the ITT population of IMvigor130. Further research is needed to understand which patients might benefit from first-line combination treatment. No new safety signals were observed.”
Matthew D. Galsky, MD, of Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 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.
