The US Food and Drug Administration (FDA) today approved atezolizumab (Tecentriq, Genentech, Inc), the first cancer immunotherapy that acts as a programmed cell death ligand inhibitor (PD-L1), for the treatment of urothelial carcinoma, the most common type of bladder cancer.

This is the first new treatment option in metastatic bladder cancer in more than 30 years, according to the manufacturer.

The drug is indicated for the treatment of patients with locally advanced or metastatic disease whose disease has progressed during or following platinum-containing chemotherapy or within 12 months of the patient's receiving neoadjuvant or adjuvant platinum-containing chemotherapy.

"Atezolizumab provides these patients with a new therapy targeting the PD-L1 pathway," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a statement.

"Products that block PD-1/PD-L1 interactions are part of an evolving story about the relationship between the body's immune system and its interaction with cancer cells," he said.

The FDA has also approved a complementary diagnostic, the Ventana PD-L1 (SP142) assay (Ventana Medical Systems), which can detect PD-L1 protein expression levels on tumor-infiltrating immune cells and help physicians determine which patients may derive the most benefit from treatment with this agent.

Clinical Data From the IMvigor210 Trial

The FDA approval was based on the results of the IMvigor 210 trial, an open-label, multicenter, phase 2 study that evaluated the safety and efficacy of atezolizumab in 310 patients with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression.

All patients received a 1200-mg intravenous dose of the agent on day 1 of 21-day cycles until unacceptable toxicity or either radiographic or clinical progression occurred.

The primary endpoint of the study was objective response rate (ORR); the median follow-up period for this cohort was 14.4 months.

The ORR was 26% for the subgroup with the highest positivity for PD-L1, 18% for the subgroup with lower positivity, and 15% for all patients.

Complete responses were seen in up to 11% of patients in the highest-positivity subgroup and in 5% of all patients. Responses were durable. The median duration of response (range, 2.1, 13.8+ months) was not reached in the cohort as a whole or in the high-positivity group (4.2, 13.8+).

For those in the lower-positivity group, the median duration of response of 12.7 months.

Median progression-free survival was 2.1 months for all patients. At 6 months, it was 30% in the highest-positivity subgroup, 17% in the lower-positivity subgroup, and 21% in the subgroup with no/minimal PD-L1 expression.

Median overall survival was 7.9 months for all patients, 11.4 months for the highest-positivity subgroup, and 6.7 months for the lowest-positivity subgroup. Twelve-month overall survival was 36% for all patients, 48% for the high group, and 30% for the low group.

The results from this trial were presented earlier this year at the at the Genitourinary Cancers Symposium 2016, as reported by Medscape Medical News.

This "may change the landscape of the treatment of the disease," said William Y. Kim, MD, from the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, during a discussion of the study.

The safety profile was acceptable, and overall, the drug was well tolerated; 65% of patients experienced an adverse event, but only 11% reported a serious adverse event.

The most common grade 3-4 adverse reactions (≥ 2%) were urinary tract infection (9%), anemia (8%), fatigue (6%), hematuria (3%), and dyspnea (4%).

In addition, three patients (0.9%) experienced either sepsis, pneumonitis, or intestinal obstruction, which led to death. Atezolizumab was discontinued because of adverse reactions in 3.2% (n = 10) of the cohort.

The FDA granted atezolizumab breakthrough therapy designation, priority review status, and accelerated approval for this indication.

According to Genentech, the drug will become available in the United States within 1 to 2 weeks.