Combination Immunotherapy Holds Promise for Patients with Rare Bladder Cancer

A woman recently came to Bradley McGregor, MD, an oncologist at Dana-Farber Cancer Institute, in severe pain with extreme fatigue. Her squamous cell bladder cancer, a rare type for which traditional treatment is generally less effective, had advanced, and it appeared that she had no other options.

But timing is everything. McGregor was conducting a 16-month clinical trial exploring the effectiveness of an immunotherapy combination drug in patients with advanced rare genitourinary cancers. She became one of 55 to join; within weeks her symptoms had improved. A CT scan showed a remarkable response to therapy, during which she was able to spend time with her young family.

Unfortunately, 18 months later, the cancer started to grow again — but in that time she had “an amazing quality of life” that she may not have had otherwise, recalls McGregor, clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber/Brigham and Women’s Cancer Center.

Bradley McGregor, MD.

Strikingly, 37 percent of patients with rare advanced bladder cancers within that phase II multisite study responded well to nivolumab and ipilimumab, a combination therapy that in 2018 became the standard of care to treat kidney cancer. (The study was led by Dana-Farber and published in November in Cancer.) And two patients in the study, which took place between April 2018 to July 2019, are still responding well to the drug long after they stopped treatment.

“It’s certainly very exciting and may offer a new treatment option for this unmet need,” McGregor adds.

Given the exciting results, the trial is testing the combination in another 24 patients and is recruiting patients now. If it continues to be effective, the combination could one day become the first line of treatment for patients with rare bladder tumors.

Treating multiple tumors

While the overall response rate of all patients in the study across three subsets of genitourinary cancers was just 16 percent, the promising results prompted McGregor to zero in, specifically, on the subset of rare bladder cancers. The findings are a beacon of hope for those with rare cancers who’ve historically had little opportunity to enroll in clinical trials since there are so few of them.

“These patients are coming to a place like Dana-Farber because they want to get a novel therapy, and unfortunately, there have been very few options for them,” says McGregor.

Given the tumor agnostic approach to immunotherapy — that these drugs had already been approved or showed promise in preclinical studies across a variety of tumor types with common mutations as opposed to a specific tissue type — the researchers decided to use the combination on rare tumor types to see if we could find a novel effective approach.

Both nivolumab and ipilimumab, which fall into a class of drugs called immune checkpoint inhibitors, are now successfully treating a number of different cancers in addition to kidney cancer. They do this by blocking the proteins that turn off the T cells that kill cancer.

This was the first immunotherapy treatment for all patients in the study.

“Until now, there’s been minimal data to help guide these patients,” says McGregor. “This study really highlights an unmet need, and at the end of the day, it gives us insight into these diseases and novel approaches that can then be expanded.”

This study took place in conjunction with MD Anderson Cancer Center, Emory University, Ohio State University, University of California San Diego, and Beth Israel Deaconess Medical Center.