The immunotherapy atezolizumab (Tencetriq, Genentech) has been granted an accelerated approval by the US Food and Drug Administration (FDA) for first-line use in the treatment of metastatic urothelial cancer (mUC) in patients who are not eligible for cisplatin.
This is an area of unmet need, the company noted, pointing out that up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment.
Bladder cancer is the most common type of urothelial carcinoma, which also includes cancers of the urethra, ureters, and renal pelvis.
This latest labeling is an expansion of the indications for atezolizumab, which is already approved for second-line use in patients with locally advanced urothelial carcinoma or mUC who have experienced disease progression during or following any platinum-containing chemotherapy, as well as for neoadjuvant use (within 12 months of receiving chemotherapy before surgery) and adjuvant use (after surgery) in mUC.
In addition, the drug is approved for metastatic non–small cell lung cancer.
Atezolizumab was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer, and it was the first major advance in the field for 30 years. "It 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," the company stated.
Two other immunotherapies are in clinical trials for bladders cancer – nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co). All three drugs act on the programmed cell death pathway, and experts have said that they are already "altering the landscape" for the treatment of bladder cancer.
Early Data Suggest Clinical Benefit
The accelerated approval granted for first-line use is based on data from the phase 2 IMvigor210 trial, an open-label, multicenter, single-arm study.
Study participants were enrolled into one of two cohorts. The new approval is based on results from cohort 1, which consisted of 119 people with locally advanced urothelial cancer or mUC who were ineligible for cisplatin-containing chemotherapy and either had not been previously treated or had experienced disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. This cohort received atezolizumab 1200 mg intravenously every 3 weeks until either unacceptable toxicity or disease progression.
The primary endpoint of the study was objective response rate, which was seen in 23.5% of patients. Complete responses were seen in 6.7%, and partial responses were seen in 16.8%.
The manufacturer notes that the most common grade 3-4 adverse reactions were fatigue (8%), urinary tract infection (5%), anemia (7%), diarrhea (5%), increased creatinine levels (5%), intestinal obstruction, increases in liver enzyme levels (4%), hyponatremia (15%), decreased appetite (3%), sepsis, back/neck pain (3%), renal failure, and hypotension. Five people (4.2%) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure, or respiratory distress, which led to death. One patient (0.8%) experienced herpetic meningoencephalitis and disease progression at the time of death. Atezolizumab was discontinued because of adverse reactions in 4.2% of patients.
Genentech notes that it is conducting a confirmatory phase 3 study (IMvigor211), in which atezolizumab is being compared to chemotherapy in both first-line and second-line settings.