The following article, written by Melissa Pozotrigo, Senior Clinical Oncology Pharmacist at Oncology Analytics, is the final of a four-part series on key trends and findings from the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, held May 29-31, 2020.
Bladder cancer, also referred to as urothelial cancer, develops when healthy cells in the bladder lining (urothelial cells) grow uncontrollably and form a tumor. Although this cancer is most commonly found in the bladder, it can occur in other parts of the urinary tract. Most patients with bladder cancer are diagnosed at an early stage when it is highly treatable; however, even early-stage bladder cancer may recur or advance to a higher stage. Patients with bladder cancer that has spread to other parts of the body (metastasized) have a poor prognosis, with a five-year survival rate of only about 5%.
According to the American Cancer Society, it is estimated 81,400 adults in the United States will be diagnosed with bladder cancer and 17,980 deaths will occur from this disease in 2020. Bladder cancer mostly affects older adults and is more common in men. World renowned singer, actor, and producer Frank Sinatra suffered from bladder cancer. He lived his final years in poor health, ultimately succumbing to a heart attack at the age of 82.
Since 2016, the Food and Drug Administration (FDA) has approved five unique immunotherapy drugs for metastatic bladder cancer. They belong to a class of medications known as immune checkpoint inhibitors. Avelumab is a checkpoint inhibitor known as a programmed death-ligand 1 (PD-L1) blocking antibody; it works by releasing a natural brake on the immune system so that immune cells recognize and attack tumors. Until recently, avelumab was only approved for bladder cancer as second-line therapy in patients with advanced or metastatic disease who progressed on platinum-based chemotherapy or progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
While most patients with advanced bladder cancer have disease control with first-line platinum-based chemotherapy, progression-free survival and overall survival are short because of the emergence of chemotherapy resistance. After first-line chemotherapy, only 25% to 55% of patients receive second-line treatment. Even then, outcomes with second-line therapy remain suboptimal because of rapid disease progression.
At ASCO 2020, exciting results from the phase 3 JAVELIN Bladder 100 trial were presented. This randomized, multi-center study evaluated avelumab as maintenance therapy following response or stable disease with first-line platinum-based chemotherapy in patients with advanced or metastatic urothelial cancer (UC). The primary endpoint was overall survival (OS). In total, 700 patients were randomized (1:1) to receive either avelumab plus best supportive care (BSC) or BSC alone. The median OS with avelumab plus BSC vs. BSC alone was 21.4 vs. 14.3 months, respectively. This OS benefit was observed irrespective of whether a patient’s tumors expressed high levels of PD-L1, which is the target of avelumab. The most common adverse effects in the avelumab group included urinary tract infections, anemia, back pain, and fatigue.
As a result, avelumab was granted approval by the FDA on June 30, 2020, for maintenance treatment of patients with locally advanced or metastatic UC that has not progressed with first-line platinum-containing chemotherapy. Importantly, this marks a major milestone in this arena. The significant improvement in OS seen in this study enabled a pivotal change in the treatment paradigm for UC. First-line maintenance treatment with avelumab should now be considered the new standard of care for patients with advanced UC who have not progressed on platinum-based induction therapy regardless of PD-L1 status.
Key advancements such as the Javelin Bladder 100 trial, along with other studies currently underway, are paving the road so that more patients will hopefully be on the winning side of the battle with bladder cancer.