Genentech, a member of the Roche Group announced that the US Food and Drug Administration (FDA) granted accelerated approval to Tecentriq (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Urothelial carcinoma accounts for 90 per cent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.

“Tecentriq is a new medicine that can work with the immune system to treat people with a type of bladder cancer that progressed after platinum-based chemotherapy,” said Sandra Horning, M.D., chief medical officer and head of global product development. “We thank the scientists, doctors, patients and their families who made it possible to bring Tecentriq to people with advanced urothelial carcinoma.”

"Even though bladder cancer is the fifth most commonly diagnosed cancer in the United States, it hasn’t received the same attention within the cancer community as other common cancers,” said Diane Zipursky Quale, president and co-founder, Bladder Cancer Advocacy Network. “Tecentriq is a new medicine for people whose locally advanced or metastatic bladder cancer has progressed on platinum-based chemotherapy and may have limited treatment options.”

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 tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Today’s approval of Tecentriq is based on the phase II IMvigor 210 study.

Possible serious side effects with Tecentriq include, but are not limited to, lung problems (pneumonitis), liver problems (hepatitis), intestinal problems (colitis), hormone gland problems (especially the pituitary, thyroid, adrenal glands and pancreas), nervous system problems (neuropathy and meningoencephalitis), eye problems, severe infections and severe infusion reactions.

Genentech is also evaluating Tecentriq in a confirmatory phase III study (IMvigor 211), which compares Tecentriq to chemotherapy in people whose bladder cancer has progressed on at least one prior platinum-containing regimen.

IMvigor 210 is an open-label, multicenter, two-cohort phase II study that evaluated the safety and efficacy of Tecentriq in people with locally advanced or mUC, regardless of PD-L1 expression. People in a cohort of the study 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 (n=310) received a 1200-mg intravenous dose of Tecentriq on day one of 21-day cycles until unacceptable toxicity or either radiographic or clinical progression. The primary endpoint of the study was objective response rate (ORR) as assessed by an independent review facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included duration of response (DOR). A summary of the efficacy and safety data from the IMvigor 210 study that supports this accelerated approval is included below. The median follow-up time for this cohort was 14.4 months.

In a subset of people in the IMvigor 210 study with disease progression following neoadjuvant or adjuvant platinum-containing therapy (n=59), Tecentriq shrank tumors (ORR) in 22.0 per cent (95 per cent CI: 12.3, 34.7) of people.

The most common Grade 3-4 adverse reactions (= 2 per cent) were: urinary tract infection (9 per cent), anemia (8 per cent), fatigue (6 per cent), dehydration, intestinal obstruction (partial or complete blockage of the bowel), urinary obstruction, hematuria (blood in the urine; 3 per cent), dyspnea (difficulty breathing; 4 per cent), acute kidney injury, abdominal pain (pain in stomach area; 4 per cent), venous thromboembolism (blood clots in the vein), sepsis (blood infection) and pneumonia (lung infection). Three people (0.9 per cent) experienced either sepsis, pneumonitis (lung problems) or intestinal obstruction, which led to death. Tecentriq was discontinued for adverse reactions in 3.2 per cent (10) of the 310 patients.
About metastatic urothelial carcinoma

According to the American Cancer Society (ACS), it is estimated that more than 76,000 Americans will be diagnosed with bladder cancer in 2016. About 11 per cent 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 per cent of people will live five or more years when diagnosed with the earliest stage of the disease, compared to 39 per cent 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.

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of 350 in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine.

Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1. Atezolizumab is designed to bind to PD-L1 expressed on tumor cells and tumor-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.