ASCO 2019: Comparing First-Line Treatments in Poor-Prognosis Metastatic Prostate Cancer
Posted: Wednesday, June 26, 2019
The use of cabazitaxel in the first-line treatment of patients with poor-prognosis metastatic castration-resistant prostate cancer seems to provide more of a clinical benefit than abiraterone or enzalutamide. In addition, circulating tumor DNA (ctDNA) and genomic alterations were found to be prognostic. Kim N. Chi, MD, FRCPC, of the University of British Columbia, and colleagues presented updated results from their phase II study at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 5003).
In total, 95 patients with poor-prognosis and/or greater than 3 poor-prognosis criteria were randomly assigned to receive either cabazitaxel or androgen receptor (AR)-targeted therapy (abiraterone or enzalutamide). Of the patients included in the study, 18% had liver metastasis, 88% had early castration-resistant prostate cancer, and 30% had more than 3 criteria for a poor prognosis.
Th median progression-free survival was 5.8 months for patients treated with cabazitaxel and 3.1 months for patients treated with either AR-targeted therapy, although it was not statistically significant. The mean overall survival was greater for patients treated with cabazitaxel, 37 months compared with 15.5 months. The clinical benefit rate was 88% for those assigned to cabazitaxel and 70% for patients assigned to either abiraterone or enzalutamide.
A baseline ctDNA fraction higher than 15% was associated with both shorter first-line progression-free survival (2.8 months vs. 8.4 months) and overall survival (14 months vs. 38.7 months). Common ctDNA alterations included mutations in AR (53%), TP53 (45%), PI3K pathway (31%), RB1 (23%), and DNA repair (21%). Shorter progression-free survival was also seen with AR gain and TP53 defects. Patients with defects in both TP53 and RB1 tended to have worse progression-free and overall survival than patients with a TP53 mutation alone.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.
