Researchers have found that combining the immunotherapy drug pembrolizumab with standard chemotherapy may improve treatment outcomes in patients with small cell bladder cancer and small cell/neuroendocrine prostate cancer, according to a recent study published by Gu et al in Cell Reports Medicine.
Background
Small cell carcinomas—which can arise in tissues of the bladder, prostate, lungs, ovaries, and breasts—are known for their rapid progression, tendency to relapse following initial treatment, and poor overall survival rates. Patients with advanced small cell bladder cancer typically survive for just 7 to 13 months, and those with small cell/neuroendocrine prostate cancer tend to survive for just 7 to 9 months.
Immune-based treatment such as pembrolizumab has demonstrated success in treating patients with a variety of advanced or metastatic cancers, including those with advanced small cell lung cancer. Previous laboratory-based research has revealed that small cell cancers in the bladder, lungs, and prostate may share many biological traits.
Study Methods and Results
In the early-stage study, the researchers pursued the concept that treatment approaches should target cancers based on molecular similarities. They designed a clinical trial across all small cell/neuroendocrine urologic cancers combining pembrolizumab and chemotherapy as a first-line therapy for small cell bladder and prostate cancers. The researchers recruited 15 patients who were separated into two cohorts: those with advanced or metastatic small cell bladder cancer (n = 7) and those with primary small cell/neuroendocrine prostate cancer (n = 8). The study was designed for patients who would routinely receive chemotherapy as part of their standard care.
The researchers showed that 43% of the patients who received the combination of pembrolizumab and chemotherapy achieved a partial or complete regression of disease, and 86% of patients with bladder cancer and 57% of those with small cell/neuroendocrine prostate cancer survived 2 years.
The patients showed favorable responses. In the bladder cancer group, about 14% (n = 1/7) experienced disease progression after a median follow-up of nearly 3 years. In the prostate cancer group, the median survival among patients with small cell/neuroendocrine prostate cancer reached 27 months, which was longer than expected compared with the historical average.
The combination treatment was also reported to be well tolerated, with no patients needing to stop therapy as a result of side effects. Along with the encouraging survival rates, the researchers discovered that the clonal expansion of CD8-positive T cells in the blood in response to treatment seemed to correlate with better progression-free survival.
Conclusions
The results supported the need for larger clinical trials to confirm the findings.
“The combination of pembrolizumab and chemotherapy presents a promising new treatment approach for these challenging-to-treat, rare cancers and could be a major breakthrough for patient care,” highlighted senior study author Arnold Chin, MD, PhD, Professor of Urology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), as well as a member of the UCLA Health Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “These results suggest that the combination therapy could provide a substantial survival benefit,” he concluded.
Disclosure: For full disclosures of the study authors, visit cell.com.
