Nivolumab, Gemcitabine, and Cisplatin for Patients With Muscle-Invasive Bladder Cancer Undergoing Cystectomy

Dr. Shah: Welcome to PracticeUpdate. I’m your host, Dr. Aman Shah, and I’m delighted to be here with Dr. Shilpa Gupta from the Cleveland Clinic. Welcome, Shilpa.

Dr. Gupta: Thank you, Dr. Shah.

Dr. Shah: So, we’re here at ASCO GU, and you are presenting a very interesting trial on neoadjuvant treatment in bladder cancer. Could you tell us what the standard care right now is in neoadjuvant treatment?

Dr. Gupta: Yeah, so right now, the standard-of-care treatment for neoadjuvant therapy in muscle-invasive bladder cancer is cisplatin-based combination chemotherapy, either with gemcitabine and cisplatin or MVAC, and most commonly we use gemcitabine and cisplatin in this place. And our trial, BLASST-1, the Bladder Cancer Signal Seeking Trial, was looking at addition of immunotherapy to the standard-of-care chemotherapy combination in this setting.

Dr. Shah: Okay, and so what specific drugs did you evaluate?

Dr. Gupta: So, we looked at nivolumab and gemcitabine and cisplatin for four cycles prior to radical cystectomy.

Dr. Shah: Okay, and what did you find?

Dr. Gupta: Yeah, so we enrolled 41 patients over a year and we found that the downstaging at radical cystectomy occurred in 66% of patients. These were patients who had muscle-invasive disease, including clinical T2 to T4A and N1 disease, and our primary endpoint was any downstaging to less than muscle-invasive disease at cystectomy, so these results are pretty exciting, to see 66% of downstaging, and we also saw that complete pathological responses occurred in 49% of patients status pT0 and carcinoma in situ at cystectomy.

Dr. Shah: So, that is quite promising. Now, I know that in practice defining exactly what constitutes muscle invasive can be problematic, so how exactly would you suggest that clinicians apply this in their practice, if at all?

Dr. Gupta: So, typically patients undergo TURBT and in that biopsy is what we usually rely on if it invades the muscle, but many times if the tumor is really big sometimes the biopsy may show muscle is not involved, even though clinically it’s D3. So, we really need to integrate the clinical as well as the pathological staging to define what the stage is.

Dr. Shah: Okay, and I also understand that in practice there are differences between using cisplatin versus carboplatin for bladder cancer. Could you describe those and what you would recommend in these patients?

Dr. Gupta: Right, so for metastatic disease carboplatin is routinely used for patients who are not eligible to receive cisplatin. For the neoadjuvant setting, we usually do not use carboplatin because it is felt it’s very inferior and there’s an unnecessary delay to radical cystectomy in this curative setting. So if patients are not considered eligible for cisplatin, we recommend upfront cystectomy for those patients as a standard of care.

Dr. Shah: That makes a lot of sense. Well, thank you so much, and hopefully this will improve our standard of care.

Dr. Gupta: Thank you.