The US Food and Drug Administration (FDA), in a latest press release on May 18, 2016, has approved atezolizumab injections for the treatment of urothelial carcinoma. This drug can now be administered to patients suffering from locally advanced or metastatic types of carcinoma. Atezolizumab  is the first drug of its kind to get an accelerated approval for indications of this cancer.

Atezolizumab is available in the injection form and will be marketed under the trade name ‘Tecentriq’. It is the research product of Genentech, Inc, San Francisco, California.

After the green signal from FDA, the drug will be administered to patients of urothelial carcinoma with disease progression during or after the platinum-based chemotherapy. Additionally, it can be used in neo-adjuvant therapy cases to reduce the tumor size before surgery and in adjuvant therapy cases, combined with chemotherapy to eradicate the tumor altogether. In adjuvant cases combined with platinum chemotherapy, the drug usually takes 12 months to slow down disease progression.

Richard Pazdur, MD, and the Director at Hematology Office and Oncology Products, FDA Centre for Drugs Evaluation and Research, said, “Atezolizumab provides these patients with a new therapy targeting the PD-L1 pathway.” He further stated that, “The products that block PD-1/PD-L1 interactions are part of an evolving story about the relationship between the body’s immune system and its interaction with cancer cells.”

Grounds On Which This Approval Has Been Granted

The approval for atezolizumab’s use in urothelial carcinoma is based on the clinical trials data. These trials were multi-centered, single-armed, two cohort and phase 2 clinical trials. For this purpose, 310 patients suffering from either locally advanced or metastatic type of urothelial carcinoma were selected. All the patients previously received adjuvant or non-adjuvant platinum-based chemotherapy for treatment of their disease. Disease progression was observed within 12 months after the platinum containing chemotherapy. In some of the cases, the progression was observed during the therapy.

The patients with any type of autoimmune disorders requiring immunosuppressive drugs were also excluded from the trials. They were then administered with 1,200 mg dose of atezolizumab injection as an IV infusion after every three weeks. The major parameters that were observed during the trials included confirmed objective response rate (ORR) and duration of the response (DoR). These parameters were observed by an independent review facility (IRF).

Out of the selected patients, 78% were presented with visceral metastasis. In 19% of the patients, the disease progressed after the adjuvant or non-adjuvant therapy. 40% of the total patients received at least two prior therapies for their advanced cancer.

The findings of the trials indicated that the confirmed objective response rate (ORR) for all patients was 14.8%. The duration of the response ranged from greater than 2.1 months to greater than 13.8 months. The median DoR was not attained and it was observed that out of 46 responders, 37 demonstrated an ongoing response for ≥ 6 months while in 6 patients, it was observed to be ≥ 12 months. The tumor specimens of the patients were examined using Ventana PD-L1 (SP142) assay kit. On the basis of the examination, the patients were divided into two subgroups: one considered as PD-L1 positive if the stained tumor immune cells occupied an area of ≥5% at the tumor site and the other having PD-L1 expression less than 5%. Out of 310 patients, only 32% patients were identified as PD-L1 positive and the rest of 68% patients demonstrated the PD-L1 expression less than 5%. In the 100 patients that were PD-L1 positive, the confirmed optical response rate (ORR) was observed to be 26%, whereas in the remaining 210 patients having the PD-L1 expression <5%, it was 9.5%. The duration of the responses for both of these subgroups were same.

On the basis of all the positive results exhibited by atezolizumab, the FDA first granted a breakthrough therapy designation and a Priority Review Designation on March 14, 2016. Now, this drug has got an accelerated approval for treating advanced urothelial carcinoma.

About Atezolizumab And Urothelial Cancer

Atezolizumab (Tecentriq) is an injectable monoclonal antibody that acts by blocking programmed death ligand (PD-L1). This PD-L1 is overexpressed on the tumor cells and by blocking its activity, the tumor growth and progression may be decreased. This antibody is now the first one to get an FDA approval for treating metastatic and locally advanced urothelial cancer. The dose recommended for Atezolizumab is 1,200mg, which can be given as an IV (intravenous) infusion for a time of over 60 minutes, after every three weeks.

The therapy is continued until the signs of disease progression appear or unacceptable toxicity occurs in the body. The common adverse drug reactions which were observed with this drug during the clinical trials included loss of appetite, fatigue, lethargy, nausea, symptoms of constipation, infections of urinary tract and fever. Severe to life-threatening adverse reactions were observed in almost 50% of the selected patients for the trials. The other adverse effects that were observed with the use of atezolizumab included hepatitis, colitis (inflammation of colon), pneumonitis (inflammation of lungs), adrenal insufficiency, development of thyroid disease, pancreatitis, skin rash or contact dermatitis and diabetes.

The FDA has also approved an additional diagnostic kit for the testing of PD-L1 expression testing on tumor-infiltrating immune cells. This kit is called Ventana PD-L1 (SP142) by Ventana medical systems, Inc, Arizona, USA. This kit can be useful in determining the effectiveness of the drug therapy and the disease progression in the patients. The testing may also be helpful for the physicians in the selection of the patients for this drug therapy.

The urothelial cancer is a type of bladder cancer and constitutes almost 90% of all the bladder cancer cases. This carcinoma can also develop in the pelvic region, ureters and urethra.