Study: Immunotherapy Following Chemotherapy Shows Extended Survival of Patients with Advanced Urothelial Cancer

Study results presented during the virtual science program at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting found that the immunotherapy drug avelumab improved overall survival of patients with advanced urothelial cancer by 7.1 months more than the best supportive care following chemotherapy.

According to researchers, these results are the largest survival benefit seen to date in this patient population in the maintenance setting. Bladder cancer is among the top 10 causes of cancer-related deaths in the United States, and this study was the first to demonstrate efficacy of front-line treatment in the period after initial chemotherapy.

According to the study results, when combined with best supportive care, avelumab resulted in a median overall survival of 21.4 months compared with 14.3 months for best supportive care alone.

Avelumab is a checkpoint inhibitor monotherapy that functions by blocking the programmed death-ligand 1 (PD-L1) protein on the surface of cancer cells. Once those proteins are blocked, the body is better able to identify and target those cancer cells.

“The maintenance setting is an attractive time for using a checkpoint inhibitor,” said Thomas Powles, MD, director of Barts Cancer Centre in London, in a statement. “Patients have gone through chemotherapy and the disease is under control. But instead of waiting for disease to progress after chemotherapy—which is will quickly do in patients with advanced urothelial cancer—adding avelumab significantly improves survival.”

Participants in the trial had unresectable locally advanced or metastatic urothelial carcinoma, with no disease progression following chemotherapy. Of the 700 participants, 350 were randomized to receive maintenance avelumab with best supportive care while the other half received best supportive care alone. Approximately half (51%) had tumors that were positive for PD-L1.

In addition to the overall responses, the investigators examined responses in the group of patients with tumors that were positive for PD-L1. According to the press release, avelumab plus best supportive care significantly prolonged overall survival in this group, with a median overall survival not yet established. The median overall survival was 17.1 months for patients who received best supportive care alone.

Finally, the researchers noted that progression-free survival was better with avelumab and best supportive care for all patients and those with PD-L1-positive tumors, compared with best supportive care alone.

“In urothelial cancer, patients have high PD-L1 expression and high tumor mutational burden,” Powles said. “Response rates associated with immune therapy are pretty high. This means that checkpoint inhibitors can work quite well in urothelial cancer.”

Grade 3 or higher adverse events occurred in 47.4% of the patients who received avelumab plus best supportive care, compared to 25.2% in those who received best supportive care alone. The most common grade 3 or higher adverse events were urinary tract infection, anemia, hematuria, fatigue, and back pain.

REFERENCE

Immunotherapy Following Chemotherapy Offers Extended Survival to Patients with Advanced Urothelial Cancer [news release]. American Society of Clinical Oncology; May 28, 2020. https://www.asco.org/about-asco/press-center/news-releases/immunotherapy-following-chemotherapy-offers-extended-survival. Accessed June 2, 2020.