ESMO Virtual Congress 2020: Treatment in CARD Eligible Metastatic Castration Resistant Prostate Cancer Patients According to the Status of Germline HRR Mutations: Cabazitaxel vs Enzalutamide/Abiraterone

To address this question, the authors identified patients recruited to the PROREPAIR-B (NCT03074735) study that met enrollment criteria for the CARD study. PROREPAIR-B is a prospective multicentric study examining the prognostic role of germline deleterious mutations in HRR genes and the efficacy of therapies in mCRPC in the context of these HRR mutations. Of the 419 patients in PROREPAIR-B, 95 met CARD eligibility criteria. Of these patients, 14 had germline alterations in HRR genes. Relative to CARD, the cohort for this study was more likely to have ECOG PS 2 patients who received abiraterone as first line therapy. This cohort, similar to CARD, had prolonged radiographic progression free survival (6 vs 3.7 months, p = 0.03) and PSA50 response (39% versus 17%, p = 0.027) with cabazitaxel over alternative anti-androgen therapy. No overall survival difference was seen in this cohort.

When stratified by germline HRR status, HRR mutation carriers had worse outcomes with regards to overall survival (HR 1.9), radiographic progression free survival (2.4) and clinical progression-free survival (HR 2.6) relative to patients without germline HRR mutations. Using cox multivariate analysis, a significant interaction was observed between germline HRR mutations and response to cabazitaxel for radiographic and clinical progression free survival.

The authors concluded that their data confirms the superiority of cabazitaxel therapy over alternate anti-androgen therapy, similar to CARD. In this small cohort, patients with germline HRR mutations seemed to not derive benefit from cabazitaxel relative to the alternative therapy, but overall outcomes in this cohort were rather poor. This data should be interpreted in the context of another presentation at ESMO 2020, suggesting that cabazitaxel has efficacy in patients with certain alterations detected in HRR genes by tumor tissue profiling. Additional data may be helpful in determining the optimal sequencing of cabazitaxel versus Olaparib in mCRPC patients who have progressed on docetaxel and at least one anti-androgen therapy.