Abstract 628P
Background
The CARD trial proved that in mCRPC patients (pts), previously treated with docetaxel and an androgen-receptor signaling inhibitor (ARSi), cabazitaxel (CBZ) significantly improves progression-free (PFS) and Overall Survival (OS) compared with the alternative ARSi. Concurrently, the PROFOUND trial showed that in men with mCRPC who had progressed while receiving ARSi harboring also alterations in Homologus Recombination DNA repair related genes (HRR), olaparib improves PFS and response comparing with a subsequent ARSi.
Methods
PROREPAIR-B is a prospective study which evaluated the prognostic role of germline deleterious mutations in (g)HRR genes and the impact on mCRPC outcomes. In this study, we evaluated radiographic (r)-PFS, clinical (c)-PFS, and OS in PROREPAIR-B pts who meet CARD study eligibility criteria and who received CBZ and/or ARSi. Survival analysis were performed using Kaplan Meier method and Cox regression models.
Results
Of the 419 mCRPC pts included in PROREPAIR-B, 95 met CARD eligibility criteria and received CBZ (n=60) or ARSi (n=35) after 1/2L, including 14 gHRR carriers, 8/6 treated with CBZ/ARSi respectively. In contrast with CARD trial, ECOG 2, M1 at diagnosis, abiraterone as 1st ARSi and prior radiographic progression were more frequent in our series of pts (all p<0.05). Overall, CBZ demonstrated a greater benefit over ARSi in terms of rPFS (median 6.0 vs 3.7 months (m), p=0.03), cPFS (median 4.4 vs 3.4 m, p=0.01) and PSA50 response (39% vs 17%, p=0.027). No differences in terms of OS were observed between the two groups. Overall, gHRR carriers had a significant worse prognosis (OS HR 1.9; rPFS HR 2.4; cPFS HR 2.6) comparing with non-carriers. In gHRR carriers, CBZ treatment was not superior to ARSi in terms of rPFS (2.5 vs 3.0 m, p=0.8), cPFS (2.5 vs 2.4 m, p=0.8) and OS (4.5 vs 3.7, p=0.8).
Conclusions
The results of our study confirm the superiority of CBZ treatment over alternative ARSi in unselected mCRPC population. Selecting by the presence or not of alterations in gHRR, the results are generally poor regardless of treatment with CBZ or ARSi supporting the need of novel therapies in this setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
IBIMA-CNIO.
Funding
Has not received any funding.
Disclosure
C. Llacer Perez: Speaker Bureau/Expert testimony: ROCHE; Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Angelini Pharma. N. Romero Laorden: Advisory/Consultancy: IPSEN; Advisory/Consultancy: Astellas; Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Tesaro; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Sanofi. R. Lozano Mejorada: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: ROCHE; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony: Sanofi. J.M. Piulats: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen Oncology; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: VCN Biosciences; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Merck Sharp & Dohme; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): MedImmune; Research grant/Funding (self): Pfizer; Research grant/Funding (self): EMD Serono; Research grant/Funding (self): Incyte. J. Puente: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen-Cilag; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Eisai; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: Sanofi; Speaker Bureau/Expert testimony: Pierre Fabre; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Kiowa; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Lilly; Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Roche. D. Lorente Estelles: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Janssen Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer Health; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Celgene. A. Medina: Honoraria (self), Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Merck; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies: Novartis. E. Almagro: Speaker Bureau/Expert testimony: MSD; Travel/Accommodation/Expenses: BMS. P. Borrega García: Advisory/Consultancy: Bayer; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Astellas Pharma. R. Villatoro: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Pharma; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis. A. Rodriguez-Vida: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Honoraria (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self): Sanofi; Research grant/Funding (institution): Takeda; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Colvis Oncology; Travel/Accommodation/Expenses: Novartis. E. Gallardo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Pharma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer Schering Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen Oncology; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Rovi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo; Advisory/Consultancy: EUSA Pharma; Speaker Bureau/Expert testimony: LEO Pharma; Speaker Bureau/Expert testimony: Menarini; Travel/Accommodation/Expenses: Pierre Fabre. E. Castro Marcos: Honoraria (institution), Travel/Accommodation/Expenses: Astellas Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Astellas Pharma. D. Olmos Hidalgo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Honoraria (self): Sanofi; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Clovis Oncology; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Roche; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Astellas Medivation; Research grant/Funding (institution): Tokai Pharmaceuticals; Travel/Accommodation/Expenses: Ipsen. All other authors have declared no conflicts of interest.