FDA Gives Pfizer and Merck KGaA’s Bavencio a Thumbs-Up for Urothelial Cancer

The U.S. Food and Drug Administration (FDA) approved Bavencio (avelumab) for maintenance treatment of locally advanced or metastatic urothelial carcinoma (UC) that has not progressed after first-line platinum-containing chemotherapy. Bavencio is an anti-PD-L1 checkpoint inhibitor co-developed by Merck KGaA, Darmstadt, Germany and Pfizer via EMD Serono, a business unit of the two companies.

The approval was based on data from the Phase III JAVELIN Bladder 100 clinical trial. JAVELIN evaluated Bavencio and best supportive care (BSC) compared to BSC alone. A total of 700 patients were divided to receive either Bavencio plus BSC or BSC alone. The primary endpoint was overall survival (OS) in all randomized patients and in patients with PD-L1+ tumors, as determined using the Ventana SP263 biomarker assay.

Secondary endpoints included progression-free survival, anti-tumor activity, safety, pharmacokinetics, immunogenicity, predictive biomarkers and patient-reported outcomes. In the PD-L1+ patients, the risk of death was decreased by 44% in the group receiving Bavencio compared to the control arm. One patient died from sepsis, a fatal adverse reaction, in the Bavencio group. About 28% of patients receiving Bavencio reported serious adverse reactions, including urinary tract infection, pain, acute kidney injury, hematuria, sepsis, and infusion-related reactions. The most common adverse reactions were fatigue, musculoskeletal pain, urinary tract infection, and rash.

Bladder cancer is the tenth most common cancer globally, and the sixth most common in the U.S. In 2018, more than 500,000 new cases of bladder cancer were diagnosed, and killed about 200,000 people around the world. In the U.S., it is estimated that 80,470 people were diagnosed with bladder cancer in 2019, with about 12,500 locally advanced or metastatic cases diagnosed each year. Urothelial cancer (UC) makes up about 90% of all bladder cancers, and is harder to treat as it spreads through the layers of the bladder wall.

“As the first immunotherapy to demonstrate a statistically significant improvement in overall survival in the first-line setting in locally advanced or metastatic urothelial carcinoma, the FDA approval of avelumab is one of the most significant advances in the treatment paradigm in this setting in 30 years,” said Petros Grivas, one of the principal investigators in the JAVELIN Bladder 100 trial. “With median overall survival of more than 21 months measured from randomization, the longest overall survival in a Phase III trial in advanced urothelial carcinoma, the JAVELIN Bladder 100 regimen with avelumab as a first-line switch maintenance treatment has the potential to become a new standard of care based on its proven ability to reinforce the benefit (response or stable disease) of induction chemotherapy and extend the lives of patients with this devastating disease.”

Bavencio was previously approved under the FDA’s accelerated approval program in 2017 for locally advanced or metastatic urothelial carcinoma patients whose disease has progressed during or after platinum-containing chemotherapy, or whose disease had progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-based chemotherapy, based on tumor response rate and duration of response. The agency converted the accelerated approval to full approval.

“Many patients newly diagnosed with advanced urothelial carcinoma receive benefit from initial chemotherapy, but we still need treatment options that can help patients live longer,” said Andrea Maddox-Smith, chief executive officer of the Bladder Cancer Advocacy Network. “We wholeheartedly support the development of new and promising treatments as a first-line maintenance treatment until disease progression or unacceptable toxicity.”