A research team from the UCLA Health Jonsson Comprehensive Cancer Center has found that a combination of pembrolizumab, an immunotherapy drug, and standard chemotherapy can significantly improve outcomes for patients with small cell bladder cancer and small cell/neuroendocrine prostate cancer.

Small cell carcinomas are known for their aggressive nature and can develop in various tissues including the bladder, prostate, lungs, ovaries and breasts. They tend to progress rapidly, often relapse after initial treatment and have low overall survival rates. The average survival time for patients with advanced small cell bladder cancer is only about 7 to 13 months, and for patients with small cell/neuroendocrine prostate cancer, it is even shorter, at 7 to 9 months.

This new study, published in Cell Reports Medicine, found that 43% of patients treated with the combination therapy experienced either partial or complete regression of their disease. Furthermore, 86% of patients with bladder cancer and 57% of those with small cell/neuroendocrine prostate cancer lived for two years after starting the treatment. Dr. Arnold Chin, the senior author of the study and a professor of urology at the David Geffen School of Medicine at UCLA, hailed the combination of pembrolizumab and chemotherapy as a potential breakthrough for treating these rare and challenging cancers.

Pembrolizumab, an immune-based treatment, has already shown success in treating various advanced or metastatic cancers, including advanced small cell lung cancer. Previous research at UCLA, led by Dr. Owen Witte, Dr. Chin and their colleagues, revealed that small cell cancers in the bladder, lung, and prostate share many biological similarities. Based on these findings, Dr. Chin’s team theorized that treatment approaches should target cancers based on their molecular similarities, leading them to design a clinical trial combining pembrolizumab and chemotherapy as a first-line treatment for small cell bladder and prostate cancers.

The trial involved 15 patients divided into two cohorts: 7 participants with advanced or metastatic small cell bladder cancer and 8 patients with primary small cell or neuroendocrine prostate cancer. All patients were those who would typically receive chemotherapy as their standard care.

The results showed that patients responded favorably to this treatment regimen. In the bladder cancer group, only 1 out of 7 patients experienced disease progression after a median follow-up period of nearly three years. For the prostate cancer group, the median survival reached 27 months, which is significantly longer than the historical average of 7 to 9 months. Additionally, the combination treatment was well-tolerated, with no patients needing to discontinue therapy due to side effects.

Dr. Chin, who is also a member of the UCLA Health Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, believes these results indicate that the combination therapy could offer a substantial survival benefit. Interestingly, the team discovered that the clonal expansion of CD8+T cells (a type of immune cell) in the blood, in response to treatment, was associated with better progression-free survival. This suggests that a blood test could potentially predict treatment response for patients in the future.
The team emphasized that larger clinical trials are needed to confirm these encouraging findings.

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