AI Article Synopsis
- Small cell neuroendocrine cancers show similar characteristics across different tissues, often responding briefly to chemotherapy before rapidly worsening.
- A phase 1b study tested pembrolizumab combined with platinum-based chemotherapy in 15 patients, showing an overall response rate of 43% and a promising two-year overall survival rate of 86% for small cell bladder cancer and 57% for small cell prostate cancer.
- The treatment was generally well-tolerated, with 40% of patients experiencing severe side effects but no fatalities or treatment stoppages due to toxicity, alongside evidence of enhanced T cell activity linked to better outcomes.
Article Abstract
Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and T cell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse T cell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604497 | PMC |
| http://dx.doi.org/10.1016/j.xcrm.2024.101824 | DOI Listing |
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