FDA Grants Atezolizumab Accelerated Approval as Initial Treatment for Certain Patients with Advanced Bladder Cancer

First and only cancer immunotherapy approved in advanced bladder cancer as initial treatment for those unable to receive cisplatin chemotherapy

On 17 April 2017, Genentech, a member of the Roche Group, announced that the US Food and Drug Administration (FDA) granted accelerated approval to atezolizumab (TECENTRIQ®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. Atezolizumab was previously approved for patients 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 (neoadjuvant) or after surgery (adjuvant).

Bladder cancer is the most common type of urothelial carcinoma, and up to half of all patients 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.

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 tumour 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 latest approval of atezolizumab is based on the phase II IMvigor210 study.

Possible serious side effects with atezolizumab include, but are not limited to, pneumonitis, hepatitis, colitis, hormone gland problems (especially the pituitary, thyroid, adrenal glands and pancreas), neuropathy, meningitis and encephalitis, inflammation of the eyes, severe infections and severe infusion reactions.

This is the third approval for atezolizumab in under a year. Atezolizumab is also approved for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities.

About the IMvigor210 study

IMvigor210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of atezolizumab in patients with locally advanced or mUC, regardless of 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 people with locally advanced or mUC 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. Patients in this cohort received a 1200 mg intravenous dose of atezolizumab every three weeks until either unacceptable toxicity or disease progression. The primary endpoint of the study was objective response rate (ORR).

A summary of the efficacy data from the IMvigor210 study that supports this accelerated approval is included in the table below.

The most common grade 3-4 adverse reactions (≥ 2%) were: fatigue (8%), urinary tract infection (5%), anaemia (7%), diarrhoea (5%), increase in the level of creatinine in the blood (5%), intestinal obstruction, increase of the liver enzyme alanine transaminase (4%), hyponatraemia (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.

Atezolizumab is a monoclonal antibody designed to bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. Atezolizumab may also affect normal cells.