51成人动漫

This year's Genitourinary Cancers Symposium featured multiple studies on therapies in development for non-muscle-invasive bladder cancer.

In this exclusive video, Gary Steinberg, MD, from the Department of Urology at NYU Langone's Perlmutter Cancer Center in New York City, discusses several of the key abstracts in this area and their implications for clinical practice.

Following is a transcript of his remarks:

Erdafitinib [Balversa] is an FGFR3 inhibitor. We know that in non-muscle-invasive bladder cancer, especially low-grade disease, a lot of these tumors have FGFR3 alterations. We did a , and one of the cohorts we looked at was patients with carcinoma in situ, similar to what we looked at in the . One of the things is that the prevalence of FGFR3 alterations in carcinoma in situ was really unknown going into this study. We thought it would be maybe 5% in this study, it was about 10% to 15% of the patients that we screened that were FGFR3-altered with carcinoma in situ. So there were about 17 patients that we treated with oral erdafitinib. We reported on 10 patients, these were patients with BCG [bacillus Calmette-Guérin]-unresponsive carcinoma in situ, again, with very nice response rates.

The flip side, and this is where the enGene-70 is so attractive, is that the oral erdafitinib has a significant amount of toxicity, when given orally. The FGFR3 inhibitors, or erdafitinib, have been FDA approved in metastatic bladder cancer, metastatic urothelial cancer. But this is non-muscle-invasive, so you have to weigh your risks and benefits. We used a lower dose, so it's 6 mg (in the metastatic we use 8 mg, titrate to 9 [mg]), and we actually even lowered patients down to 4 mg.

In our non-muscle-invasive patients, at most we've been able to get about 3 to 4 months of therapy before patients drop off because of toxicity. Having said that, the next step in the development of non-muscle-invasive treatment with erdafitinib is to try to put the erdafitinib in something we call the TARIS pretzel. It's a delivery system, and that hopefully we can put the erdafitinib in the pretzel, which we could put inside the bladder. And so you're eliminating the potential of the systemic toxicity and getting a local distribution of the erdafitinib in the bladder, hopefully for efficacy and eliminating the toxicity. Again, that's small numbers and early data.

The other trial is looking at enfortumab vedotin [Padcev]. Enfortumab vedotin is an antibody-drug conjugate, and it is FDA approved in metastatic bladder cancer, metastatic urothelial cancer. And it's really a fascinating drug, and we're seeing results in the metastatic setting that we were never seeing with standard chemotherapy and immunotherapy. And so enfortumab vedotin has been FDA approved for patients who have metastatic advanced bladder cancer or urothelial cancer of the upper tract, did not respond to chemotherapy, did not respond to checkpoint inhibitors. And so as a third line, we're seeing some really impressive results, and we're moving the treatment earlier on into the disease processes.

So now we have an intravesical formulation, medication that we designed to put in the bladder. Again, it's a study in process. First six patients that have been treated -- again, phase I dose-escalation -- patients seem to be tolerating the intravesical enfortumab vedotin. And I have a lot of hope for this kind of approach with intravesical antibody-drug conjugates down the road.

People are also looking at sacituzumab govitecan [Trodelvy] as an antibody-drug conjugate to put in the bladder. That's under discussion and development from a number of companies, but it's another way to attack non-muscle-invasive bladder cancer: immunotherapy, cytokine delivery with EG-70, FGF targeted therapy [for] FGFR alterations, antibody-drug conjugates. Also in terms of the cytokines, we've got ImmunityBio, which has combination of . ALT803 is an IL-15 agonist, which we know supercharges or stimulates NK [natural killer] cells and some CD8 T cells to kill cancers in the urothelium. So there's just a lot of enthusiasm.

Most importantly, something that is near and dear to my heart is , which is an oncolytic vaccine. This is an adenovirus where we've put in genes, the GMCSF gene, as well as genes at the E1A, E2F promoter region. We've seen some really remarkable results with CG0070 made by CG Oncology in combination with pembrolizumab [Keytruda], intravenous pembrolizumab checkpoint inhibitor. The concept is we're creating a viral, selective immune cell death: turning on the immune system (the innate and adaptive immune system) -- interferon gamma going up causing T-cell exhaustion, hitting them with the pembrolizumab to reverse the T-cell exhaustion -- and we're seeing some excellent results.

Adstiladrin is also an oncolytic vaccine, a type V adenovirus with a couple of genes in the E1 and E3 region, as well as the type I interferon. It has been FDA approved in the BCG unresponsive space, with 25% durable response of 12 months in the carcinoma in situ patient population, BCG unresponsive. However, to date there's been manufacturing difficulties, and they're having difficulty getting the commercial manufacturing process developed so that it can become commercially available.

And then there are just a whole plethora of other agents people are thinking about, but we're clearly moving in a very exciting, innovative, 21st-century direction to help treat non-muscle-invasive bladder cancer. As we know, 75% of patients that have urothelial cancer present with non-muscle-invasive bladder cancer. The goal is to prevent it from progressing so that patients can preserve their normal urinary function, preserve their bladders, and live full normal lives.

Bladder cancer incidence worldwide is very large. It's the fourth-most common cancer among men in the U.S. -- there's about 83,000 new cases in the U.S. every year. More than that, about 150,000-plus in the EU every year. Importantly, I was with a meeting with a Chinese company, and they have about 100,000 new cases every year in China that they're reporting, with increased incidences.

So this is a significant medical issue, a medical cancer concern, and it is also a difficult and expensive cancer to treat, because of the need for frequent cystoscopies and biopsies and procedures in the operating room and so forth. If we can eliminate this cancer we certainly can save the healthcare system tremendous resources and so forth.

Comment