Combining Brachytherapy With Immunotherapy for High-Risk Prostate Cancer
Posted: Monday, August 17, 2020
Nivolumab combined with high-dose–rate brachytherapy and androgen-deprivation therapy appeared to be safe and active in patients with very high–risk prostate cancer, according to a recent proof-of-principle phase I trial published in Prostate Cancer and Prostatic Diseases. However, Kosj Yamoah, MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, and colleagues explained that the upcoming phase II trial is needed to validate these findings.
“As suggested by our preliminary analysis, the combination of androgen-deprivation therapy, anti–PD-1, and high-dose–rate brachytherapy demonstrated synergic immune activation and antitumor activity,” the investigators remarked. “This phase I/II trial targeting Grade Group 5 prostate cancer with a novel combination regimen may provide more insights into patient selection and development of new therapeutic approaches.”
A total of six patients with pathologically confirmed Grade Group 5 prostate cancer were enrolled between September 2018 and June 2019. The patients received androgen-deprivation therapy and intravenous nivolumab every 2 weeks for four cycles. High-dose–rate brachytherapy was performed after the first two cycles of nivolumab and again after the last two cycles. Subsequently, external-beam radiotherapy was delivered. The primary endpoint was to evaluate the safety and feasibility of this novel combination regimen.
Overall, the primary endpoint was met. After the second cycle of nivolumab, one patient experienced a grade 3 dose-limiting toxicity of elevated alanine aminotransferase and aspartate aminotransferase. In half the treated patients, no residual tumor was detected in at least four of six cores on biopsy. The early responders also seemed to experience an increase in CD8-positive and FOXP3-positive/CD4-positive T cells in tissues as well as CD4-positive effector T cells in peripheral blood.
Disclosure: For full disclosures of the study authors, visit nature.com.
