A new combination of cancer medications appears to extend overall survival in patients with advanced bladder cancer more than the chemotherapies currently used as the standard of care.


The research, being presented Sunday at this year’s European Society for Medical Oncology Congress in Madrid, suggests that a combination of the antibody drug enfortumab vedotin and the immunotherapy pembrolizumab, administered through IV infusions, cut the risk of disease progression or death by 55% in patients with advanced bladder cancer who hadn’t been treated before and whose cancer spread to other parts of the body — extending overall survival by a median of 31.5 months versus 16.1 months with standard chemotherapy.


This is one of several new studies exploring ways to improve how bladder cancer is treated.


“The problem with chemotherapy is although it works quite well initially, resistance occurs quickly, and the median survival for metastatic bladder cancer has been about a year,” said Dr. Thomas Powles, a professor of urology cancer at the University of London and director of the Barts Cancer Centre in the United Kingdom, who presented the research this weekend.

“What this study showed is, we did a big, randomized Phase 3 study where we compared a new treatment — two new drugs — with standard chemotherapy,” Powles said. “And in this randomized trial, when you gave those two drugs together, you reduced the risk of death for this cancer by over 50%. So, you’ve doubled survival, with patients living twice as long, and we’ve got long-term durable remission.”


Globally, bladder cancer is the sixth most common cancer in men and the disease kills about 200,000 people every year, many of whom die from advanced disease that has spread beyond the bladder. Treatment options typically depend on the stage of disease but may include surgery or common chemotherapy drugs, such as carboplatin or cisplatin.


And the new research findings — funded by the US drugmakers Seagen, Inc., Astellas Pharma and Merck & Co. — come at a time when the United States is experiencing a significant shortage of platinum-based chemotherapy drugs, including carboplatin and cisplatin.


The Phase 3 trial included 886 patients who were randomly assigned to receive either three-week cycles of the enfortumab vedotin and pembrolizumab combination, administered as IV infusions, or a chemotherapy treatment called gemcitabine with cisplatin or carboplatin.


The trial found that the new drug combination had a similar safety profile as the chemotherapies, with adverse reactions such as skin rashes or hyperglycemia occurring in 55.9% of patients taking the combination compared with 69.5% of those taking platinum chemotherapy.


“We only got the data three weeks ago, so it’s happening just very, very quickly,” Powles said, adding the next step for the research team is to submit their data to the US Food and Drug Administration and other agencies around the world. The data has not yet been published in a peer-reviewed journal.“Because it’s so conclusive, we don’t need to do a larger study. We now need to transform this into patients quickly, so we need to go to the agencies — the FDA in the United States, the EMA in Europe and around the world,” he said. “We need to get this approved quickly.”


The research findings by Powles and his colleagues have the potential to change the standard of care for advanced bladder cancer, said Dr. Toni Choueiri, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, who was not involved in the new paper but is attending the ESMO Congress in Madrid.


“Ever since I was in med school, a metastatic bladder cancer treatment was gemcitabine and platinum. Gemcis or GemCarbo, we called it. Since the late ’90s, nothing beat that in frontline. But now, the combination of pembrolizumab, an immunotherapy checkpoint blocker, and enfortumab vedotin, an antibody-drug conjugate, beat — hands down — the old regimen that we have had since the late 1990s,” Choueiri said. “I think this is going to become a new standard.”


Another approach with longer survival

Some other new studies have evaluated new ways to treat a different set of advanced bladder cancer patients — those whose disease continued to progress after trying one or two previous treatments.


Another Phase 3 trial found that a targeted therapy was effective for patients with advanced or metastatic urothelial cancer who had specific gene mutations. Urothelial cancer is a type of bladder cancer that begins in the urothelial cells, which line the inside of the bladder. Almost all bladder cancers are urothelial carcinomas.