Patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for Platinol (cisplatin) treatment will now have access to Genentech‘s immune checkpoint inhibitor Tecentriq (atezolizumab) in the United States.
The accelerated approval granted by the U.S. Food and Drug Administration is meant for either previously untreated patients or for those who had disease progression at least 12 months after chemotherapy. It follows a 2016 accelerated approval of Tecentriq for mUC patients whose disease progressed during or following platinum-based chemotherapy.
Continued approval for these indications may be contingent upon verification and description of clinical benefit in future confirmatory trials.
“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,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said in a news release.
“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,” she said.
The recent approval was based on data from Cohort 1 of the IMvigor210 Phase 2 trial (NCT02951767), a single-arm study designed to evaluate the safety and effectiveness of Tecentriq in locally advanced or metastatic urothelial bladder cancer. Participants in the study were included in one of two cohorts.
Cohort 1 enrolled 119 mUC patients who were ineligible for Platinol-based chemotherapy and were either previously untreated or had disease progression at least 12 months after receiving chemotherapy, administered before or after surgery.
Patients received Tecentriq (1,200 mg) every three weeks until disease progression or unacceptable toxicity. The study’s primary endpoint was objective response rate (ORR), deemed as the proportion of patients who achieved either a partial or a complete response to Tecentriq.
Among the 119 participants, 28 patients responded to treatment, including eight complete responses, amounting to an ORR of 23.5% and a complete response rate of 6.7%.
While the complete responses did not vary with the levels of PD-L1, the findings showed that patients with PD-L1 expression of 5% or higher had better partial response rates (21.9% PR) — and thus ORR — than those with PD-L1 expression below 5% (14.9% PR).
The most common grade 3 or 4 adverse events included fatigue, urinary tract infection, anemia, diarrhea, intestinal obstruction, and increase in liver and kidney enzymes. Five patients died from treatment side effects, which included sepsis, cardiac arrest, heart attack, and respiratory failure. Five patients discontinued treatment due to adverse side effects.
“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, CEO of the 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.”
Genentech is currently evaluating Tecentriq in the confirmatory IMvigor211 Phase 3 trial (NCT02302807), which is comparing Tecentriq with chemotherapy as a first-line treatment for mUC patients who progressed during or following a platinum-based regimen.