Following standard chemotherapy, Avelumab was found to increase the overall survival of patients with advanced urothelial bladder cancer.
According to the North American Association of Central Cancer Registries, more than 80,000 Americans will be diagnosed with bladder cancer in 2022 with an anticipated loss of 17,000 patients to the disease. Most of these cases are urothelial cancer, which forms along the lining of the urinary tract. Nonurothelial cancer, which affects the mucus-secreting glands in the bladder, remains rare, affecting less than 5 percent of bladder cancer patients.
Jeanny Aragon-Ching, MD, Clinical Program Director of Genitourinary Cancers at Inova Schar Cancer Institute, participated in two multi-institutional studies to better understand bladder cancer.
The first study explored trends in urothelial cancers that occur in the upper tract of the urinary system and bladder as well as nonurothelial cancers diagnosed between 2004 and 2017. The information was gathered from the National Cancer Database. This study included 649,939 cases, of which 630,423 were urothelial cancer and 19,516 were nonurothelial cancer.
More nonurothelial cancer cases were identified at stage IV (about 22 percent) compared to urothelial cases (about 5 percent), suggesting a more advanced presentation. The standard treatment for both types of cancer is chemotherapy, and survival outcomes for urothelial cancers are better than for nonurothelial counterparts. As such, the cases of urothelial cancers, although more common, had better prognoses. Following the regular course of chemotherapy, immunotherapy is given upon the reoccurrence or worsening of cancer. The study saw the opportunity to explore additional treatments for both forms of bladder and upper tract cancer.
Dr. Aragon-Ching also participated in the multi-institutional JAVELIN Bladder 100 clinical trial. The trial explored the effectiveness of the drug avelumab along with best supportive care in improving the survival rate of patients with advanced urothelial bladder cancer that has spread beyond the urinary tract.
“This trial changed the landscape of treatment,” said Dr. Aragon-Ching. “The concept of maintenance didn’t happen until this trial and [the results have] changed the way we treat metastatic bladder cancer.”
Avelumab is a type of immunotherapy. It attaches to a protein called PD-L1 that is found on the surface of many types of cancer. Avelumab acts like a beacon, helping the body’s immune cells find and destroy cancer cells. The drug was found to be safe for long-term use in patients.
The clinical trial recruited patients with advanced urothelial bladder cancer after receiving four to six cycles of chemotherapy. The patients who responded positively to the initial, standard therapy and found their tumors remained stable or diminished in size were enrolled in the trial.
Of the 700 participants in the trial, half were placed in the group that received avelumab maintenance treatment plus best supportive care. The remaining participants received the standard best supportive care, which includes treatments that help manage symptoms but do not affect the cancer.
Dr. Aragon-Ching and her colleagues followed the trial participants for two years.
The researchers found that avelumab extended the overall survival of patients compared to those only receiving the best supportive care. In fact, participants who received avelumab and best supportive care lived an extra nine months (an average of 24 months compared to 15 months). In addition, 23 percent of the patients in the avelumab group showed no sign of disease progression compared to 7 percent in the best supportive care group.
While many of the participants in the trial were PD-L1 negative, the treatment remained effective. According to Dr. Aragon-Ching, this may be due in part to the use of archival tumor tissue when typing the cancer, because the test may not be a perfect biomarker.
“The PD-L1 biomarker is fluid and may not necessarily predict who will respond to treatment,” said Dr. Aragon-Ching. “The results of this trial suggest that we should not deny patients who are PD-L1 negative this treatment.”
The U.S. Food and Drug Administration approved avelumab in 2020. It is now considered the standard maintenance treatment for people with advanced urothelial cancer after receiving chemotherapy when they have stable disease.
“These results solidify our understanding of the treatment landscape of metastatic bladder cancer,” said Dr. Aragon-Ching. “The next question is, how can we further improve on these results and get better outcomes beyond maintenance?”
Request an appointment with Inova Schar Cancer Institute or learn more about the Inova Genitourinary Cancer Program.