(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a session on navigating urothelial carcinoma from innovative diagnostics to therapeutic strategies, and a presentation by Dr. Borivoj Golijanin discussing pembrolizumab in BCG refractory non-muscle invasive bladder cancer and the association of adverse events with discontinuation of treatment.
Non-muscle invasive bladder cancer is associated with high rates of recurrence and progression despite primary treatment with BCG. The KEYNOTE-057 trial reported 41% complete response after 3 months and low rates of adverse effects (13% grade >= 3) in patients treated by pembrolizumab for BCG refractory non-muscle invasive bladder cancer [1]. In January 2020 pembrolizumab was approved by the FDA for the treatment of high-risk non-muscle invasive bladder cancer that has not responded to BCG treatment in patients and who cannot or do not want to have a radical cystectomy. This study, presented at EAU 2024, reports results of a single institution’s experience using pembrolizumab in BCG refractory patients with high-risk non-muscle invasive bladder cancer.
This study included patients with non-muscle invasive bladder cancer who were treated with pembrolizumab between January 2020 and January 2023 at a single institution. Demographic and clinicopathologic information was collected, and Kaplan-Meier curves were generated to calculate progression-free survival and treatment-specific survival. The combined positive score of PD-L1 was assessed for each case treated with pembrolizumab.
Among 250 patients with non-muscle invasive bladder cancer who were screened for the study, 18 met the inclusion criteria. The median age was 74.5 years (IQR 67.8 – 81.4), the male-to-female ratio of 3.5:1, the median follow-up time was 17.5 months (IQR 8.1 – 22.5), and all had a prior history of CIS and had been treated with intravesical chemotherapy after becoming BCG refractory. At the start of pembrolizumab, stage distribution was as follows: 1 (5.6%) cTa, 6 (33.3%) CIS, and 11 (61.1%) cT1. After a median of 9 cycles (IQR 6 – 16), 72.2% stopped treatment, and 28.2% are still undergoing treatment, with an average of 12.6 cycles (SD 10.4). Overall, 1 out of the 13 patients who stopped treatment had a complete response. The remaining reasons for termination of treatment were Grade 2 or higher immune-related adverse events in 53.8%, progression in 30.8%, and recurrence in 7.7%. Recurrence-free survival rates at 3-, 6-, and 12-months were 16.7%, 11.1%, and 5.6%, respectively. The disease progression free survival curve is as follows:
The median treatment-specific survival was 26.5 months (SD 2.9). Four patients ultimately required radical cystectomy which revealed one each of pTa, pTis, pT1, and pT4. Only 1 patient had combined positive score of PD-L1 > 10.
Dr. Golijanin concluded his presentation discussing pembrolizumab in BCG refractory non-muscle invasive bladder cancer and the association of adverse events with discontinuation of treatment with the following statements:
- More research is needed to improve the identification of patients who are likely to benefit from this treatment
- Pembrolizumab for BCG refractory non-muscle invasive bladder cancer in the real world setting is highly toxic, poorly tolerated, and associated with unsatisfactory oncological outcomes
- Early discussion about radical surgery remains an important part of the treatment guidelines for BCG refractory non-muscle invasive bladder cancer
Presented by: Borivoj Golijanin, MD, The Miriam Hospital and Warren Alpert Medical School of Brown University, Providence, RI
Written by: Zachary Klaassen, MD, MSc - Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, WellStar MCG Health, @zklaassen_md on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
References: