FDA Grants Priority Review for Atezolizumab in First-Line Treatment of Patients With Urothelial Carcinoma Who are Not Eligible for Cisplatin Chemotherapy

Second priority review granted for atezolizumab in advanced bladder cancer

On 8 January, 2017Genentech, a member of the Roche Group announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for atezolizumab (TECENTRIQ®) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are ineligible for cisplatin chemotherapy, and are either previously untreated (first-line) or have disease progression at least 12 months after receiving neoadjuvant or adjuvant chemotherapy.

Urothelial carcinoma accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra. About 11% of new diagnoses are made when bladder cancer is in advanced stages. There is a dramatic difference in survival rates between early and advanced bladder cancer. Approximately 96% of patients will live five or more years when diagnosed with the earliest stage of the disease, compared to 39% when diagnosed in advanced stages (stage III-IV) of the disease. Men are about three to four times more likely to get bladder cancer during their lifetime than women.

In May 2016, atezolizumab became the first treatment approved by the FDA for patients with previously treated advanced bladder cancer in more than 30 years.

This sBLA submission for atezolizumab is based on results from the phase II IMvigor210 study, and the FDA will make a decision on approval by 30 April, 2017. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease.

Atezolizumab is currently approved by the FDA to treat patients with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy or whose disease has worsened within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. Atezolizumab is approved under accelerated approval for this indication 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.

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.

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. Cohort 1, upon which this sBLA submission is based, consisted of patients who were ineligible for first-line cisplatin-based chemotherapy, and who had received no prior chemotherapies for locally advanced or mUC (i.e., first-line) or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. Cohort 2, which served as the basis for the FDA’s accelerated approval of atezolizumab in May 2016, included patients whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen, or who had disease progression within 12 months of treatment with a platinum-based neoadjuvant or adjuvant chemotherapy regimen. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included duration of response (DOR), overall survival (OS), progression-free survival (PFS) and safety.

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. It may also affect normal cells.

Atezolizumab can cause serious side effects, including pneumonitis, hepatitis, colitis, hormone gland problems (especially the pituitary, thyroid, adrenal glands and pancreas), nervous system problems (neuropathy, meningitis, encephalitis), inflammation of the eyes, severe infections, severe infusion reactions.

The most common side effects of atezolizumab in previously-treated patients with urothelial carcinoma include feeling tired, decreased appetite, nausea, urinary tract infection, fever, constipation.

Atezolizumab may cause fertility problems in females.

These are not all the possible side effects of atezolizumab.