First-Line Atezolizumab Active in Metastatic Urothelial Carcinoma

First-Line Atezolizumab Active in Metastatic Urothelial Carcinoma

Dr. Arjun Vasant Balar
First-line treatment with the immune checkpoint inhibitor atezolizumab resulted in durable responses in patients with metastatic urothelial carcinoma who were ineligible for cisplatin, according to the primary analysis results of the IMvigor210 cohort 1 (Abstract LBA4500) presented during the Genitourinary (Nonprostate) Cancer Oral Abstract session on Sunday, June 5.

With a median follow-up of 14.4 months, there was an objective response rate of 24% (95% CI [16%, 32%]) and a median overall survival of 14.8 months.

“The median survival observed so far is quite compelling and makes the argument that atezolizumab should be the standard of care for cisplatin-ineligible patients,” presenter Arjun Vasant Balar, MD, of Perlmutter Cancer Center, NYU Langone Medical Center, told the ASCO Daily News.

According to Dr. Balar, there have not been a lot of major advances in therapy for first-line treatment of bladder cancer in the last few decades. Currently, cisplatin-based chemotherapy is the standard of care in the first-line setting; however, many patients are ineligible for cisplatin because of renal impairment, poor performance status, or other comorbidities. For many cisplatin-ineligible patients, treatment with carboplatin is a viable alternative, but response and survival with carboplatin are inferior to cisplatin.

Atezolizumab is a monoclonal antibody targeting PD-L1. In cohort 1 of the IMvigor210 study, 119 patients were assigned to 1,200 mg atezolizumab every 3 weeks until RECIST v1.1 disease progression. Patients were ineligible for cisplatin therapy and were chemotherapy naive in the metastatic setting. PD-L1 expression on tumor-infiltrating immune cells (ICs) was assessed by immunohistochemistry and scored as IC 0, 1, or 2/3.

With a median follow-up duration of 14.4 months, the objective response rate was 24%, with 7% of patients achieving complete response and 17% achieving a partial response. The analysis showed that response, including complete response, occurred in all IC subgroups. Among patients with a score of IC 2/3, there was a 28% response rate, and among the underexpressing group (score, IC 0), there was a 21% response rate, with 8% of patients achieving complete response. The disease control rate was 31% in all patients.

“Activity of this level in this population is unprecedented,” Dr. Balar said during his presentation.

Responses were rapid, occurring at a median time of approximately 2 months, and they were durable, Dr. Balar said. At the data cutoff, 75% of responses are ongoing. The researchers also observed tumor regression in all IC subgroups including 63% of patients in the IC 0 subgroup. The estimated 12-month overall survival rate was 57%, and the event-to-patient ratio at this point was 47%.

Dr. Elizabeth R. Plimack
Overall, atezolizumab was well tolerated with a low rate of treatment-related grade 3/4 adverse events and discontinuations due to adverse events (6%). No declining kidney function was observed in patients with preexisting kidney impairment. There was one treatment-related death from sepsis.

The rate of grade 3/4 immune-related adverse events that required steroids was also very low (6%), and no patients were treated with non-corticosteroid immunomodulatory agents for immune-related adverse events.

According to Dr. Balar, the next step will be to conduct a randomized trial to test atezolizumab with or without chemotherapy to establish if the benefits seen here persist.

Commenting on the results, discussant Elizabeth R. Plimack, MD, MS, of Fox Chase Cancer Center, told the ASCO Daily News, “The results of the single-arm trial of first-line atezolizumab in the cisplatin-ineligible metastatic urothelial population are intriguing in that while the response rates are not superior to historic controls, the median overall and benchmark 1-year survival is better than what we have seen in the past with chemotherapy in this population. Further investigation in a randomized setting is needed to define whether PD-1 inhibition is best used first line.”

– Leah Lawrence