Avelumab may improve survival in Urothelial Cancer, finds Phase III Trial

Researchers from Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center and University of Washington Medicine have conducted a global phase III JAVELIN Bladder 100 randomized study to evaluate  role of avelumab in metastatic urothelial cancer.

The results demonstrated significantly prolonged overall survival of patients with locally advanced (unresectable) or metastatic urothelial cancer when treated with first-line immunotherapy avelumab plus best supportive care (BSC) compared to BSC alone (following disease control on induction chemotherapy).

The findings of the study will be presented in a plenary session of the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The JAVELIN Bladder 100 phase III clinical trial compared maintenance treatment with avelumab plus BSC with BSC alone on patients with locally advanced/unresectable or metastatic urothelial (arising from bladder and other parts of urinary tract) cancer that did not worsen during or following completion of first-line induction chemotherapy. Results show that avelumab increases overall survival, making this a new potential standard of care for thousands of people with urothelial cancer worldwide.

"Our findings should give hope to many patients with advanced urothelial cancer who face a very challenging and difficult condition," said Petros Grivas, MD, PhD, Associate Professor and Clinical Director of the Genitourinary Cancers Program at SCCA, Associate Professor, Division of Medical Oncology University of Washington School of Medicine and global co-principal investigator in the JAVELIN Bladder 100 trial. "People with advanced urothelial cancer generally have a poor prognosis, and most experience cancer progression (growth) within eight months after initiation of first-line chemotherapy. We are very excited with these results, which indicate that immunotherapy with avelumab first-line maintenance could offer a new treatment option that helps patients live longer. Even if this is likely not a complete cure and may cause potential side effects in some patients, the significant prolongation of overall survival is clearly a remarkable improvement, while many treated patients may not experience significant side effects from this approach."

JAVELIN Bladder 100 was a multicenter, multinational, randomized, open-label, parallel arm trial. Seven hundred patients with locally advanced/unresectable or metastatic urothelial cancer received 4-6 cycles of first-line 'induction' platinum-based chemotherapy which is usually administered over a period of 3-5 months. Those whose disease had not progressed were randomized to receive avelumab with BSC or BSC alone. Avelumab with BSC demonstrated 31% reduction in risk of death and median overall survival of 21.4 months versus 14.3 months with BSC alone, measured from the time of randomization.

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody co-developed and co-commercialized by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. In April 2020, it received U.S. Food and Drug Administration Breakthrough Therapy Designation for first-line maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma.

The National Cancer Institute's Surveillance, Epidemiology and End Results program estimates that approximately 81,400 cases of bladder cancer will be diagnosed only in the U.S. in 2020. Bladder cancer is the tenth leading cause of cancer death in the U.S., and the five-year survival rate for its metastasized forms is only about 5%. Urothelial carcinoma accounts for approximately 90% of all bladder cancers and can also arise from the kidney, pelvis, ureters, and urethra.

SCCA's Bladder Cancer Multispecialty Clinic, comprised of specialists with broad and deep clinical and research expertise in bladder and other urinary tract (urothelial) cancer, offers advanced treatment options and innovative clinical trials and provides cancer care to hundreds of patients each year.