FDA Approves Tecentriq for Metastatic Bladder Cancer

Based on data from a phase 2 study, Tecentriq (atezolizumab), a PD-L1 inhibitor, was granted an accelerated approval for patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.

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The approval was based on data from the phase 2 IMvigor 210 study, in which Tecentriq had an overall response rate (ORR) of 14.8 percent in patients with locally advanced or mUC, regardless of PD-L1 expression. Among patients with PD-L1 expression at least 5 percent, ORR was 26 percent. The PD-L1 assay Ventana PD-L1 (SP142) was concurrently approved as a complementary

“Tecentriq provides these patients with a new therapy targeting the PD-L1 pathway,” Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “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.”

IMvigor 210 enrolled an all-comer population of 316 patients with inoperable locally advanced or mUC. Data from 310 patients were evaluable; the mean patient age was 66 years, 78 percent were male, and 62 percent of patients had ECOG PS 1. The site of primary tumor was the bladder for 75 percent of patients with metastasis to viscera reported for 78 percent of patients and to the liver in 31 percent of patients.

All patients had progressed during or following platinum-based chemotherapy. The patients had been heavily pretreated, with 40 percent of patients undergoing two or more prior systemic regimens in the metastatic setting and 74 percent of patients receiving previous cisplatin-based chemotherapy.

Tumor tissue was prospectively assessed centrally for PD-L1 expression using the SP142 immunohistochemistry assay. PD-L1 status was assessed on tumor cells and immune cells using an SP142 antibody-based immunohistochemistry assay; however, both the patients and investigators were blinded as to PD-L1 status. Tecentriq was administered at 1,200 mg intravenously on the first day of each 21-day cycle until no further clinical benefit was demonstrated. Median treatment duration was 12 weeks. The coprimary study endpoints were ORR, as assessed by central review and the investigators, both by modified RECIST v1.1. Secondary endpoints included duration of response, progression-free survival, overall survival and safety.

At a median follow-up of 14.4 months, ORR was 14.8 percent in all comers, 26 percent in patients with PD-L1 expression at least 5 percent, and 9.5 percent in those with PD-L1 expression less than 5 percent. In a subgroup of 59 patients from the IMvigor 210 study who progressed after neoadjuvant or adjuvant platinum-based chemotherapy, the ORR was 22 percent.

Complete response rates in the overall, higher—PD-L1, and lower–PD-L1 groups were 5.5 percent, 12 percent and 2.4 percent, respectively. Partial response rates were 9.4 percent, 14 percent and 7.1 percent, respectively. The median duration of response was 12.7 months in the higher PD-L1 population, and had not yet been reached in either the overall group or the lower PD-L1 cohort.

Overall, 10 patients discontinued Tecentriq due to adverse events (AEs). The most common grade 3/4 adverse events included urinary tract infection (9 percent), anemia (8 percent), fatigue (6 percent), dyspnea (4 percent) and hematuria (3 percent). There were three patient deaths, which were related to sepsis, pneumonitis or intestinal obstruction.

Tecentriq previously received a breakthrough therapy designation from the FDA for the treatment of patients with PD-L1—positive metastatic bladder cancer. The accelerated approval is contingent on results from an ongoing confirmatory phase 3 study, IMvigor 211 (NCT02302807), which is comparing Tecentriq with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer who have progressed on at least one prior platinum-containing regimen.

“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,” Sandra Horning, chief medical officer and head of Global Product Development at Genentech, the manufacturer of Tecentriq, said in a statement. "We thank the scientists, doctors, patients, and their families who made it possible to bring Tecentriq to patients with advanced urothelial carcinoma.”