ASCO GU 2019: Discussion on: Results of Checkmate 650 and Circulating Tumor Cell Number as a Transitional Surrogate Endpoint for Survival in mCRPC Trials
Sipulecel-T is the only immunotherapy currently approved in patients with mCRPC. Previous trials have shown no improvement in outcomes for PROSTVAC and GVAX. Ipilimumab also did not demonstrate survival benefits in patients who were chemotherapy naïve asymptomatic or minimally symptomatic or post-docetaxel and bone-directed radiotherapy. KEYNOTE 199 (pembrolizumab in the post-docetaxel setting for mCRPC) only showed a PSA response of 19%. Nivolumab with Ipilimumab has been studied and published in the New England Journal of Medicine in the advanced renal cell and melanoma settings, demonstrating improvements in overall survival.
Analysis of the presented data demonstrated that Nivolumab with Ipilimumab has clinical activity in patients with mCRPC. Specifically, better responses are seen in patients with less advanced disease and positive biomarkers. Furthermore, the median time to response is short, which may impact long term data outcomes.
In the second half of this session, Dr. Kelly analyzed Dr. Sher’s circulating tumor cell (CTC) biomarker study. Most CTCs die in circulation due to physical or oxidative stresses, with an overall lack of growth factors or cytokines present for support. A small percentage of CTCs can develop a metastatic lesion, with the ability to exhibit features of an epithelial to mesenchymal transition. Previous studies have shown that >5 CTCs/7.5ml of blood in prostate cancers is associated with a poor prognosis and post-treatment decline to <4 CTCs/7.5ml is associated with improved survival.
Previous trials published in the Journal of Clinical Oncology support CTCs as a potential surrogate for survival in mCRPC and may be a better predictor than PSA. This study demonstrated that CTC0 response had a higher likelihood to predict overall survival compared to PSA50. The goal of these analyses is to develop a short term outcome biomarker to shorten drug development time, reduce costs of clinical trials, increase the number of treatments that can be evaluated, and to improve clinical management. However, further studies are needed to assess these response endpoints to possibly broaden development in other phases of prostate cancer or even other malignancies.
Presented by: William Kevin Kelly, DO, Professor, Sidney Kimmel Cancer Center, Jefferson University Hospital, Philadelphia, Pennsylvania
Written by: David B. Cahn, DO, MBS, @dbcahn, Fox Chase Cancer Center at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA