Yesterday the US Food and Drug Administration granted accelerated approval to the new anti-PD-L1 immunotherapy atezolizumab, which is sold as TECENTRIQ™ by Genentech Inc., for treating a type of bladder cancer that has seen no new therapies in about 30 years.

Accelerated approval, which is for medications for which there is an unmet need and demonstrable early clinical benefit, was based on the phase II open-label, multicentre, two-cohort IMvigor 210 trial to determine the safety and efficacy of atezolizumab in locally advanced or metastatic urothelial carcinoma patients regardless PD-L1 expression who had progressed within 12 months of adjuvant or neoadjuvant platinum-based chemotherapy (the second cohort, n=310). [Lancet 2016.pii:S0140-6736(16)00561-4]

These patients (median age 66 years, 78 percent male) received 1,200 mg infusions of atezolizumab every 3 weeks until unacceptable toxicity or radiographic or clinical progression, with median follow-up of 14.4 months.

Compared to a historical control overall tumor response rate of 10 percent, atezolizumab had an objective response rate (ORR) of 14.8 percent (p=0.0058). Patients with higher PD-L1 expression performed better than patients with lower PD-L1 expression (ORR 26 percent vs 9.5 percent, respectively).

In all patients complete response was 5.5 percent. Median duration of response was not reached in all patients or in the high PD-L1 expressing subgroup and was 12.7 months in the low PD-L1 expressing subgroup.

The most common grade 3-4 adverse reactions included urinary tract infection, nausea, and fatigue and there were no treatment-related deaths.

“This report is the first to show the association of The Cancer Genome Atlas subtypes with response to immune checkpoint inhibition and to show the importance of mutation load as a biomarker of response to this class of agents in advanced urothelial carcinoma,” the researchers said.

Results from the first cohort of the IMvigor 210 trial are not yet released and may clarify response durability. Roche, which owns Genentech and funded the IMvigor trials, has an ongoing phase III trial to compare atezolizumab to standard of care chemotherapy in metastatic urothelial cancer who progressed after initial treatment.