Study results presented at the 2022 American Urological Association Annual Meeting showed that the regimen of pembrolizumab (Keytruda) plus cabazitaxel (Jevtana) and gemcitabine had promising early efficacy in heavily pretreated patients with high-risk non–muscle invasive urothelial carcinoma (NMIUC).1
In an interview at the meeting, lead study author Vignesh Packiam, MD, urologist, assistant professor of Urology, University of Iowa Hospitals and Clinics, discussed the retrospective analysis.
Packiam: This project is looking at outcomes of a novel regimen for patients with treatment refractory, non-muscle invasive bladder cancer. This is looking at 2 different endoluminal agents, which are gemcitabine, and cabazitaxel in conjunction with an intravenous agent, pembrolizumab
Our institution has had good success utilizing gemcitabine and docetaxel, which are 2 different chemotherapies used sequentially. It was initially explored for patients with BCG unresponsive disease. Although now with the persistent BCG shortage, we've evaluated this more and more for BCG naive bladder cancer as well. We've noticed that even though the response rate to this agent is very promising, there are some patients that have recurrences to this regimen as well.
We were looking for an effective salvage option for patients who recurred despite receiving gemcitabine/docetaxel. We know from prostate cancer that resistance can eventually form from exposure to docetaxel. In those patients, cabazitaxel is an alternative agent, which has shown to have some efficacy. That was the rationale for utilizing gemcitabine and cabazitaxel within the urinary system.
At the same time, there has been a recent FDA approval of pembrolizumab, which is an intravenous checkpoint inhibitor, although there are concerns about suboptimal long term efficacy. The 1-year complete response for pembrolizumab monotherapy is only 19%, so our hope was with combining these agents, we could develop a more effective treatment regimen for these patients.
This regimen was offered to patients who were heavily pretreated. The median number of prior complete intravascular inductions was for in this cohort. It was a heavily pretreated population of patients who either had too many comorbidities considered to be a reasonable surgical candidate for cystectomy or a patient who had been refusing radical cystectomy. We looked back over the past 2 years for patients who have received this regimen and retrospectively identified 13 patients who received this regimen with a total of 18 treated units. Thirteen were bladder, and 15 renal units, which were which had the presence of carcinoma on side 2 or positive cytology.
We found that at initial evaluation, which was a restaging procedure performed at 3 months, there was an 86% complete response rate in the overall cohort with 89% complete response when you're considering each unit separately for the upper tracks and the bladder. The 3-month evaluation was fairly thorough with cystoscopy in situ performed for all patients, random bladder biopsies, prostatic urethral biopsies, and upper tract washings. When we continued surveillance at 6 and 12 months, we noticed that the complete response rate was 79% for patients at 6 months, and 50% for patients at 12 months, which is relatively favorable and promising compared to other agents in this type of paper patient population.
We noticed that there was significant bladder toxicity that developed in 5 of these patients. Some of this may have been a result of their heavy pre-treatment history, with alternative regimens used prior to them receiving this treatment regimen. A few patients had to have treatment holidays from the gemcitabine side cabazitaxel to allow their bladders to recover. One patient did require a cystectomy due to end stage bladder symptoms. The optimal dosing is definitely something that we're still exploring.
This study has transitioned into a prospective protocol through our cancer center where we are going to more rigorously look for the optimal dosing regimen. It is something that's exciting and I think it's going to help us figure out the efficacy of this regimen and additionally evaluate safety and dosing parameters.
1. Packiam V, McElree I, Steinberg RL, et al. Sequential endoluminal cabazitaxel and gemcitabine with pembrolizumab for docetaxel-unresponsive non-muscle invasive urothelial carcinoma of the upper and lower urinary tracts. Presented at: 2022 American Urological Association Annual Meeting; May 13-16. New Orleans, LA. Abstract PD26-07