FDA Approves Second Indication for Bavencio as Bladder Cancer Treatment

Immunotherapy also treats Merkel cell carcinoma

The FDA has approved avelumab injection (Bavencio, EMD Serono/Pfizer) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or after platinum-containing chemotherapy, or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Avelumab was previously granted accelerated approval for the treatment of adult and pediatric patients 12 years of age and older with metastatic Merkel cell carcinoma.

Avelumab was designed to potentially engage both the adaptive and innate immune systems. By binding to programmed death ligand 1 (PD-L1), avelumab is thought to prevent tumor cells from using PD-L1 for protection against leukocytes, such as T cells, exposing them to antitumor responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity in vitro.

The efficacy and safety of avelumab were demonstrated in the urothelial carcinoma cohorts of the JAVELIN Solid Tumor trial, a phase 1, open-label, single-arm, multicenter study that included 242 patients with locally advanced or metastatic urothelial carcinoma with disease progression during or after platinum-containing chemotherapy or who had experienced disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen.

Patients were included regardless of their PD-L1 status. The patients received avelumab at a dose of 10 mg/kg intravenously over 60 minutes every two weeks until disease progression or unacceptable toxicity occurred. Tumor-response assessments were performed every six weeks. Efficacy outcome measures included the confirmed overall response rate, and the duration of response. Efficacy measures were evaluated in patients who were followed for a minimum of both 13 weeks and six months at the time of data cut-off.

The efficacy and safety findings will be presented at an upcoming medical congress.

The warnings and precautions for avelumab include immune-mediated adverse reactions (including pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, and renal dysfunction); infusion-related reactions; and embryo-fetal toxicity. The most common adverse events in patients with locally advanced or metastatic urothelial carcinoma included fatigue (41%), infusion-related reactions (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infections (21%).

In December 2015, a phase 3, multinational, randomized, open-label, parallel-arm trial (JAVELIN Bladder 100) was initiated to evaluate avelumab plus best supportive care versus best supportive care alone as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma whose disease did not progress after completion of first-line platinum-containing chemotherapy. This study is currently enrolling patients.

Source: Pfizer; May 9, 2017.