Atezolizumab Misses Disease-Free Survival End Point in Muscle-Invasive Urothelial Cancer

January 24, 2020

Atezolizumab failed to meet the primary end point, disease-free survival, as adjuvant monotherapy in patients with muscle-invasive urothelial cancer compared with observation in the phase III IMvigor010 clinical trial, according to a press release from Roche, developer of the drug.

Atezolizumab (Tecentriq) failed to meet the primary end point, disease-free survival (DFS), as adjuvant monotherapy in patients with muscle-invasive urothelial cancer (MIUC) compared with observation in the phase III IMvigor010 clinical trial, according to a press release from Roche, developer of the drug.

“Reducing the risk that muscle-invasive urothelial cancer will recur after surgery is very difficult, and we are disappointed that we were not able to significantly prolong disease-free survival,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche. “We remain committed to exploring the potential benefits of immunotherapy for more people with early cancers.”

Despite not meeting its primary end point, IMvigor010 demonstrated a consistent safety profile for atezolizumab based on previous studies for this drug. No new safety signals were identified with the drug in this clinical trial.

IMvigor010 is a global, open-label, randomized, controlled clinical trial that was designed to evaluate the safety and efficacy of atezolizumab as an adjuvant therapy in patients with MIUC who are at high risk for recurrence following resection, and the drug was compared with observation. DFS was defined as the time from randomization to invasive urothelial cancer recurrence or death.

Ongoing and planned phase III clinical trials are evaluating atezolizumab as a single agent or in combination as treatment for patients with both early- and advanced-stage bladder cancer. However, by treating MIUC earlier, the risk of disease recurrence or spreading can be reduced. Nearly half of the patients with MIUC, which is generally associated with a poorer prognosis, will recur within 2 years of surgery, leading to a need for additional treatment options following therapy.

More than 500,000 new cases of bladder cancer were diagnosed in 2018 across the globe,whereas200,000 deaths occurred from this disease. MIUC spreads to the muscle of the bladder, ureter, or renal pelvis in patients with urothelial cancer, which is the most common type of bladder cancer. Urothelial cancer accounts for between 90% to 95% of all cases of bladder cancer, and about 25% of all cases are diagnosed as MIUC.

Atezolizumab, a monoclonal antibody targeting PD-L1, is an immunotherapy that presents the potential to be used both alone/in combination with other therapies across a number of cancer types. It has previously been approved either alone or in combination with targeted therapies or chemotherapies for a variety of cancer types, including non—small cell lung cancer, metastatic urothelial cancer, and PD–L1-positive metastatic triple-negative breast cancer. In June 2018,the FDA added PD-L1 status to the label for atezolizumab in the frontline treatment of patients with urothelial carcinomawho are platinum-ineligible, based on data from clinical trials that demonstrated lower overall survival rates in patients with low expression of PD-L1.

Reference:

Roche provides an update on phase III study of Tecentriq in people with muscle-invasive urothelial cancer [news release]. Basel: Roche; January 24, 2020. https://bit.ly/38zdRoE. Accessed January 24, 2020.