The US Food and Drug Administration ( FDA ) has granted accelerated approval to Tecentriq ( Atezolizumab ) for the treatment of people with locally advanced or metastatic urothelial carcinoma ( mUC ) who are not eligible for Cisplatin chemotherapy.
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 ( neoadjuvant ) or after surgery ( adjuvant ).
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.
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 Tecentriq 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.
Approval of Tecentriq is based on the phase II IMvigor210 study.
IMvigor210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of Atezolizumab in people with locally advanced or metastatic urothelial carcinoma, regardless of PD-L1 expression.
People 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.
People 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 ).
The most common grade 3–4 adverse reactions ( greater than or equal to 2% ) were: fatigue ( 8% ), urinary tract infection ( 5% ), anaemia ( 7% ), diarrhoea ( 5% ), increase in the level of creatinine in the blood ( 5% ), intestinal obstruction ( partial or complete blockage of the bowel ), increase of the liver enzyme alanine transaminase ( 4% ), hyponatraemia ( low blood sodium level; 15% ), decreased appetite ( 3% ), sepsis ( blood infection ), back / neck pain ( 3% ), renal failure and hypotension ( low blood pressure ).
Five people ( 4.2% ) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure or respiratory distress, which led to death.
Atezolizumab was discontinued for adverse reactions in 4.2% ( 5 ) of the 119 patients.
Roche is evaluating Atezolizumab in a confirmatory phase III study ( IMvigor211 ), which compares Atezolizumab to chemotherapy as initial treatment in people with a specific type of advanced bladder cancer and in people whose bladder cancer has progressed on at least one prior Platinum-containing regimen.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1. PD-L1 is 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. ( Xagena )
Source: Roche, 2017