FDA Grants Atezolizumab Accelerated Approval as Initial Treatment for Some Advanced Bladder Cancers


On April 17, the U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab (Tecentriq) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Atezolizumab was previously approved for people with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving neoadjuvant or after adjuvant chemotherapy.

Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters, and renal pelvis.

“We are pleased that atezolizumab 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. “Atezolizumab 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.”

“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 at the Bladder Cancer Advocacy Network. “We are excited that atezolizumab 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 FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition, based on early evidence suggesting clinical benefit. The indication for atezolizumab is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The approval of atezolizumab is based on the phase II IMvigor210 study.

About IMvigor210

IMvigor210 is an open-label, multicenter, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in people with locally advanced or metastatic urothelial carcinoma, regardless of programmed death ligand 1 (PD-L1) expression.

Patients in the study were enrolled into one of two cohorts. This accelerated approval is based on results from cohort 1, which consisted of 119 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. People in this cohort received a 1200-mg intravenous dose of atezolizumab every 3 weeks until either unacceptable toxicity or disease progression. The primary endpoint of the study was objective response rate.

Objective responses were achieved in 23.5% of patients. Results showed that 6.7% of patients achieved complete response, and 16.8% achieved partial response. The median duration of response was not yet reached.

The most common grade 3–4 adverse reactions (≥ 2%) were: fatigue (8%); urinary tract infection (5%); anemia (7%); diarrhea (5%); increase in the level of creatinine in the blood (5%); intestinal obstruction; increase of the liver enzyme alanine transaminase (4%); hyponatremia (15%); decreased appetite (3%); sepsis; back/neck pain (3%); renal failure; and hypotension. Five patients (4.2%) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure, or respiratory distress, which led to death. One additional patient (0.8%) experienced inflammation of the brain due to the herpes simplex virus (herpetic meningoencephalitis) and disease progression at the time of death. Atezolizumab was discontinued for adverse reactions in 4.2% (5) of the 119 patients.

Genentech is evaluating atezolizumab in a confirmatory phase III study (IMvigor211), which compares atezolizumab to chemotherapy as initial treatment in patients with a specific type of advanced bladder cancer and in patients whose bladder cancer has progressed on at least one prior platinum-containing regimen.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.