Major Shifts in Urothelial Cancer Care: Immunotherapy Redefines Standards

Recent advances in immunotherapy and combination therapies are revolutionizing the treatment landscape for both metastatic and muscle-invasive urothelial cancer.

In this exclusive MedPage Today video, Vadim Koshkin, MD, of the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, discusses the latest updates, including the effects of enfortumab vedotin (EV; Padcev) and pembrolizumab (Keytruda) in the metastatic setting, as well as the promising findings from the NIAGARA study for muscle-invasive bladder cancer.

Following is a transcript of his remarks:

In advanced urothelial cancer, in bladder cancer in general, there have been a lot of recent shifts in the landscape. So in the metastatic setting, as of about a year ago, the big change was the approval of enfortumab vedotin and pembrolizumab combination for patients with metastatic disease who are treatment naive — in other words, first-line treatment for metastatic urothelial cancer. This was based on the data from the EV-302 clinical trial that randomized patients to receive EV with pembrolizumab versus platinum-based chemotherapy, which was the prior standard of care. And that overturned several decades basically of prior practice.

So now most patients in the frontline metastatic setting will get [the] EV and pembrolizumab combination, and then subsequently patients in the second-line setting will usually receive platinum-based chemotherapy, as well as selected patient subsets [who] may receive FGFR inhibitors. Those are patients who have FGFR3 alterations — that’s about 15% to 20% of the population — or actually HER2-targeted agents are now available as well. This is trastuzumab deruxtecan [Enhertu], which is available for patients whose tumors have high HER2 expression, IHC [immunohistochemistry] 3+.

I should also now backtrack actually and go back to the muscle-invasive setting. So these are patients who don’t have metastatic disease but have muscle-invasive bladder cancer. And the current standard of care in this curative-intent patient population is actually platinum-based chemotherapy, followed by surgery — psoriatic cystectomy to remove the bladder. But with that, there actually has been a recent significant update at this year’s ESMO [European Society for Medical Oncology] meeting, and this was the result of the NIAGARA study.

So this study randomized patients with muscle-invasive bladder cancer, again, curative-intent patient population, to receive either cisplatin-gemcitabine, followed by radical cystectomy, which was a prior standard of care, or combination of cisplatin-gemcitabine and an immunotherapy [durvalumab (Imfinzi)] followed by radical cystectomy and then adjuvant immunotherapy as well.

This trial showed a significant benefit of the combination of immunotherapy and cisplatin-based chemotherapy, and as a result, we anticipate that this will be the new standard of care going forward. That’s not yet come to pass, as in there’s not yet an FDA approval for this combination, but we anticipate that highly likely that may happen sometime within the next calendar year.

As a result, this again will significantly shift the treatment landscape in advanced urothelial cancer. We will have to think harder about what to give in a metastatic setting to patients who may have been exposed to prior immune checkpoint inhibitors in the muscle-invasive setting.

Those are the major significant recent updates in this space, which again continues to be a very dynamic and active treatment space.