First-line treatment of metastatic urothelial carcinoma using a combination of atezolizumab and platinum-based chemotherapy is associated with significant improvement in progression-free survival and increased complete response rate, according to a new study.

The regimen also is associated with “encouraging interim overall survival data,” investigators reported in The Lancet.

The findings are from the multicenter IMvigor130 phase 3 randomized trial (NCT02807636), which enrolled 1213 patients.

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“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,” lead author Matthew Galsky, MD, Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and Professor of Medicine at the Icahn School of Medicine at Mount Sinai, said in a news release.

Dr Galsky and his collaborators randomly assigned 451 patients (37%) to receive atezolizumab, an immune checkpoint inhibitor, in addition to platinum-based chemotherapy (group A), 362 (30%) to receive atezolizumab alone (group B), and 400 (33%) to receive placebo plus platinum-based chemotherapy (group C). The median follow-up time for survival was 11.8 months for all patients. Co-primary efficacy end points were progression-free survival and overall survival (group A vs group C) and overall survival (group B vs group C).

The median progression-free survival was significantly longer in group A than group B (8.2 vs 6.3 months). The combination treatment was significantly associated with an 18% decreased risk for progression compared with the placebo arm.

Median overall survival did not differ significantly between group A and group C (16 vs 13.4 months). “Because this result did not cross the prespecified interim efficacy boundary for statistical significance (p=0.007), no further statistical hypothesis testing was done for group B versus group C.” The median overall survival did not differ significantly between group B and group C (15.7 months vs 13.1 months).

Dr Galsky’s team documented a complete response in 56 patients (13%) in group A, 22 (6%) in group B, and 27 (7%) of group C. Among patients who had a response, the median duration of response was 8.5 months.

Adverse events (AEs) leading to withdrawal of any agent occurred in 156 patients (34%) in group A, 22 (6%) in group B, and 132 (34%) in group C. In addition, 50 patients (11%) in group A, 21 (6%) in group B, and 27 (7%) in group C experienced AEs that led to discontinuation of atezolizumab or placebo.

The chemotherapy regimen consisted of 21-day cycles of gemcitabine (1000 mg/m2 body surface area, given intravenously (IV) on days 1 and 8 of each cycle, plus either carboplatin or cisplatin on day 1 of each cycle, with either atezolizumab (1200 mg administered IV on day 1 of each 21-day cycle) or placebo. Patients in group B received 1200 mg atezolizumab IV on day 1 of each 21-day cycle.

“The safety profile of the combination was consistent with that observed with the individual agents,” Dr Galsky and his colleagues concluded. “These results support the use of atezolizumab plus platinum-based chemotherapy as a potential first-line treatment option for metastatic urothelial carcinoma.”

In an accompanying editorial, Bernadett Szabados, MD, and Thomas Powles, MD, of Barts Cancer Centre in London, commented, “The IMvigor130 results presented here could be the first of several positive trials in this setting, which will have a substantial long-term impact on the treatment of advanced urothelial cancer.”

Disclosure: F Hoffmann-La Roche and Genentech funded the study.


Galsky M, Arija JAA, Bamias A, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395:1547-1557.

Szabados B, Powles T. Immune checkpoint inhibition in urothelial carcinoma. Lancet. 2020;395:1522-1523.