Article written by Bruce Sylvester
First-line platinum-based chemotherapy plus adjuvant immunotherapy with atezolizumab appears to prolong progression-free survival in patients with metastatic urothelial (bladder) cancer, researchers reported on May 16,2020 in The Lancet.
“This is the first study to show that combining chemotherapy and immunotherapy significantly delays progression of metastatic bladder cancer compared with chemotherapy alone, and the first randomized study to contextualize the use of immunotherapy alone as a first-line treatment option for patients with metastatic bladder cancer based on expression of the PD-L1 protein,” said investigator Matthew Galsky, MD, Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute in New York and Professor of Medicine at the Icahn School of Medicine at Mount Sinai Medical Center.
In this phase 3, randomized trial, the investigators enrolled an untreated subjects aged 18 years or older with locally advanced or metastatic urothelial cancer to receive atezolizumab plus platinum-based chemotherapy (group A), atezolizumab monotherapy (group B) or placebo plus platinum-based chemotherapy (group C).
Group A subjects received 21-day cycles of gemcitabine (1000 mg/m 2 body surface area, administered intravenously on days 1 and 8 of each cycle), plus either carboplatin (area under the curve of 4·5 mg/mL per min administered intravenously) or cisplatin (70 mg/m 2 body surface area administered intravenously) on day 1 of each cycle, plus atezolizumab (1200 mg administered intravenously on day 1 of each cycle) or placebo.
Group B monotherapy subjects received 1200 mg atezolizumab intravenously on day 1 of each 21-day cycle.
The primary endpoints were progression-free survival and overall survival (group A vs group C) and overall survival (group B vs group C).
The researchers enrolled 1,213 subjects. And they randomized 451 (37%) to group A, 362 (30%) to group B and 400 (33%) to group C.
Median follow-up for survival was 11.8 months.
At the time of progression-free survival analysis and interim overall survival analysis, median progression-free survival in the intention-to-treat population was 8.2 months in group A and 6.3 months in group C.
Median overall survival was 16.0 months in group A and 13.4 months in group C.
Median overall survival at the interim analysis was 15.7 months in group B and 13.1 months in group C.
Adverse events leading to withdrawal of any treatment appeared in 156 (34%) patients in group A, 22 (6%) patients in group B, and 132 (34%) patients in group C.
Fifty (11%) patients in group A, 21 (6%) patients in group B, and 27 (7%) patients in group C had adverse events that led to discontinuation of atezolizumab or placebo. The authors concluded, “Addition of atezolizumab to platinum-based chemotherapy as first-line treatment prolonged progression-free survival in patients with metastatic urothelial carcinoma. The safety profile of the combination was consistent with that observed with the individual agents. These results support the use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma.”