Treatment guidelines for bladder cancer have changed significantly in recent years, due to the introduction of effective new drug combinations to treat the disease.
That was the message from University of Colorado Cancer Center member Thomas Flaig, MD, who gave an update on bladder cancer treatment earlier this week at the National Comprehensive Cancer Network (NCCN)annual conference in Orlando.
“When immune checkpoint inhibitors for bladder cancer came out around 2016, 2017, that started to change everything,” says Flaig, who also serves as vice chancellor of research for the CU Anschutz Medical Campus. “We now have new antibody drug conjugates that are taking things by storm, and we've got a targeted agent for advanced bladder cancer as well. We have multiple new therapies and treatment options for patients based on clinical trial results.”
Winning combination
Flaig, who is chair of the NCCN Guidelines Panel for Bladder Cancer, was particularly excited to share with attendees the effectiveness of enfortumab vedotin, a new antibody drug conjugate that targets a particular marker on a bladder cancer cell, then delivers chemotherapy directly to that cell.
“It’s got an antibody that guides it to a protein called nectin-4, which is a target on bladder cancer, then it’s got a payload of a very potent chemotherapy called MMAE attached to that antibody,” Flaig explains. “The antibody is given as an IV treatment, it floats around and finds that nectin-4 marker on the cancer cell, attaches to that, and then attacks that particular cell.”
Combining enfortumab vedotin with the immune checkpoint inhibitor pembrolizumab has been particularly effective, Flaig says, with a 65% to 70% response rate in the metastatic setting across various clinical trials when used as a first-line treatment.
“Almost 30% of those were complete responses,” he adds. “It’s one thing to get a tumor that regresses; it’s another thing to get a tumor that regresses and stays regressed. There’s a notable durability to the response that we’re seeing with this combination.”
The fight continues
With an estimated 83,190 new cases of bladder cancer and 16,840 deaths from bladder cancer in 2024, according to the American Cancer Society, it’s important to keep looking for new ways to treat the disease, Flaig says. The enfortumab vedotin-pembrolizumab combination is one therapy that’s showing great promise; another is the combination of pembrolizumab with the traditional chemotherapy drug gemcitabine-cisplatin, which has shown a response rate in the mid-50% range, with a complete response rate around 20%.
“We’re seeing an integration of immune checkpoint inhibitor combination therapy in the frontline setting, in different regimens, which is one of the themes I focused on in my NCCN presentation,” Flaig says. “It's going to take more time to confirm, but there's a real hope and promise in what we're seeing in these early studies, in terms of a prolonged duration of response. It's an exciting time for patients. If I were a bladder cancer patient, I'd say, ‘They're doing research in this area. They're finding new treatments regularly. And my options as a patient are expanding.’”
Crossover potential
The effectiveness of combination therapies in bladder cancer is potentially good news for treating other cancers, Flaig says, as researchers continue to understand exactly how the drugs are working together to kill cancer cells.
“Is there a special sauce, so to speak, about this combination? Is the enfortumab vedotin working with the immune checkpoint inhibitors in a novel way to provide sustained responses? That's a big unanswered question,” he says. “If that's true, how can we emulate those results in other cancers? Can the same MMAE payload be effectively guided to a different target in another cancer type? We are using nectin-4 which is relevant to bladder cancer, but you could have a different target that’s specific to breast cancer or colon cancer, for example. This could be a plug-and-play kind of thing.”
Flaig, who also is presenting at the American Association of Cancer Research (AACR) this week, presents regularly on bladder cancer research to groups around the country, says he appreciates giving updates at the NCCN annual conference because it allows him to provide the latest information to providers who don’t always have the time to keep up with the latest in research and treatment for all types of cancer and highlight the timeliness of the NCCN guidelines in responding to therapeutic advances.
“Let's say you're a practicing oncologist in the community who doesn't treat bladder cancer very often, or it's not your main focus,” he says. “You can go to a talk like this and say, ‘I've heard there have been some things going in bladder cancer. I've seen that study; how does it fit in? How is the NCCN prioritizing this approach in the guidelines, or how is this committee evaluating these new treatment options?’
“It's a nice way for someone to get up-to-date and authoritative guidance on how they can optimally manage their patient, all in one setting. It’s more of a review and a guidelines-driven talk than a talk focused on single new research finding, and for many oncology providers, that can be very useful, especially in this time of substantial change.”
