The FDA has granted an accelerated approval to Tecentriq as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy.
The FDA has granted an accelerated approval to Tecentriq (atezolizumab) as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. The approval was announced by Genentech, the immunotherapy drug’s manufacturer.
“It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years,” said Andrea Maddox Smith, chief executive officer, Bladder Cancer Advocacy Network. “We are excited that Tecentriq is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.”
The approval is based on data from the single-arm phase II IMvigor210 trial. In a study cohort of 119 cisplatin-ineligible, treatment-naive patients, the objective response rate with Tecentriq was 23.5 percent, including a complete response rate of 6.7 percent.
Tecentriq was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery or after surgery.
“We are pleased that Tecentriq will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with cisplatin chemotherapy,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech.
“Tecentriq was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread.”
The IMvigor210 cohort enrolled 123 patients with cisplatin-ineligible locally advanced or mUC at 47 locations in North America and Europe between June 9, 2014, and March 30, 2015. Patients received 1200 mg of intravenous Tecentriq every three weeks until progression. The primary endpoint was objective response rate, with secondary outcomes measures including progression-free survival and overall survival.
Among the 123 patients, 119 received at least one dose of Tecentriq. Responses occurred regardless of PD-L1 status and across poor prognostic factor subgroups. The median duration of response was not reached. There was an association between tumor mutation load and response. The median progression-free survival was 2.7 months and overall survival was 15.9 months.
The most common grade 3/4 adverse events included fatigue (8 percent), urinary tract infection (5 percent), anemia (7 percent), diarrhea (5 percent), increase in the level of creatinine in the blood (5percent), increase of the liver enzyme alanine transaminase (4 percent), hyponatremia (15percent), decreased appetite (3 percent), and back/neck pain (3 percent).
Adverse events led to 5 patients discontinuing treatment. Five patients died, due to sepsis, cardiac arrest, myocardial infarction, respiratory failure, and respiratory distress. An additional patient had inflammation of the brain due to the herpes simplex virus and disease progression at the time of death.
The accelerated approvals of Tecentriq are contingent on results from an ongoing confirmatory phase III study, IMvigor 211 (NCT02302807), which is comparing Tecentriq with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer in the frontline setting and after progression on at least one prior platinum-containing regimen.