A research group has demonstrated that the combination of pembrolizumab, an immunotherapy drug, with standard chemotherapy can enhance treatment results for individuals suffering from small cell bladder cancer and small cell/neuroendocrine prostate cancer.
A research group led by investigators from UCLA Health Jonsson Comprehensive Cancer Center has demonstrated that the combination of pembrolizumab, an immunotherapy drug, with standard chemotherapy can enhance treatment results for individuals suffering from small cell bladder cancer and small cell/neuroendocrine prostate cancer.
Small cell carcinomas can develop in various organs, including the bladder, prostate, lungs, ovaries, and breasts. They are notorious for their rapid progression, frequent relapses post-treatment, and low overall survival rates. For patients with advanced small cell bladder cancer, the survival duration is roughly 7 to 13 months, while for those with small cell/neuroendocrine prostate cancer, it is about 7 to 9 months.
The preliminary study, published in Cell Reports Medicine, revealed that administering pembrolizumab alongside chemotherapy led to a partial or complete regression of the disease in 43% of patients. Notably, 86% of bladder cancer patients and 57% of those with small cell/neuroendocrine prostate cancer survived for two years.
Dr. Arnold Chin, a professor of urology at the David Geffen School of Medicine at UCLA and the study’s lead author, commented, “The combination of pembrolizumab and chemotherapy offers a promising new approach to treating these challenging and uncommon cancers, and it could represent a significant advancement in patient care.”
Immunotherapy, like pembrolizumab, has proven effective for patients with various advanced or metastatic cancers, including advanced small cell lung cancer. Prior laboratory research at UCLA, led by Dr. Owen Witte, Chin, and their colleagues, has shown that small cell cancers in the bladder, lung, and prostate share a number of biological characteristics. Building on these insights, Chin and his team proposed that treatment strategies should focus on the molecular similarities among cancers. They created a clinical trial examining the combination of pembrolizumab and chemotherapy as a first-line treatment for small cell cancers of the bladder and prostate.
The trial included 15 patients divided into two groups: one group consisting of seven patients with advanced or metastatic small cell bladder cancer and the other comprised of eight individuals with primary small cell or neuroendocrine prostate cancer. The study targeted patients usually recommended for chemotherapy as part of standard treatment.
Results showed that patients responded positively to this treatment regimen. In the bladder cancer group, only one of the seven patients experienced disease advancement after a median follow-up of nearly three years.
For the prostate cancer group, median survival for patients with small cell/neuroendocrine prostate cancer reached 27 months, significantly exceeding the historical average of just 7 to 9 months.
Moreover, the combination therapy was well-tolerated, with no patients needing to discontinue treatment due to side effects.
“These results indicate that this combination therapy might provide a significant survival advantage,” stated Chin, a member of both the UCLA Health Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
In addition to the promising survival rates, the research team discovered that the clonal expansion of CD8+ T cells in the blood, a particular type of immune cell responding to treatment, correlated with improved progression-free survival. This suggests that a blood test could potentially predict treatment response for patients in the future.
The findings emphasize the necessity for larger clinical trials to further validate these results.
The study’s co-lead authors are Yiqian Gu, a graduate student in UCLA’s bioinformatics interdepartmental program, and Ann Ly, a former staff researcher in UCLA’s urology department who is now a doctoral candidate at UC Davis. Contributors from UCLA also include Sara Rodriguez, Hanwei Zhang, Jiyoon Kim, Zhiyuan Mao, Ankush Sachdeva, Nazy Zomorodian, Matteo Pellegrini, Gang Li, Alexandra Drakaki, Matthew Rettig, and Sandy Liu, who is currently affiliated with City of Hope.
