Abstract 5022
Background
Subset analysis of trials investigating taxanes in patients with mCRPC suggest an association between Grade ≥3 NP and disease outcomes. In the Phase 3 PROSELICA trial (NCT01308580), NP was more common in patients receiving cabazitaxel 25 mg/m2 (C25) vs cabazitaxel 20 mg/m2 (C20) - 73% vs 42%, respectively. Post hoc analyses of PROSELICA examined the relationship between incidence of NP, survival and response.
Methods
PROSELICA assessed the non-inferiority of C20 (n = 598) vs C25 (n = 602) in terms of overall survival (OS) in men with mCRPC. Prophylactic granulocyte colony-stimulating factor was given to patients with Grade ≥3 NP. OS and progression-free survival (PFS) were analyzed using Kaplan-Meier (KM) estimates and Cox proportional hazard models. Nominal p values were determined by log-rank tests. Prostate-specific antigen response rate (PSArr; defined as proportion of patients with a > 50 % PSA decline from baseline) was analyzed in the eligible population using KM estimates with Chi2 tests and odds ratios. OS, PFS and PSArr were correlated with Grade ≥3 NP occurrence and baseline neutrophilia (neutrophils ≥7000 G/l) by univariate analysis.
Results
In the intent-to-treat (ITT) population, development of Grade ≥3 NP was associated with better PSArr, PFS and OS (p < 0.001; Table). The positive association was observed in both treatment arms and in poor-risk patients with baseline neutrophilia.Table: 811P
| Population | Outcome | Grade ≥3 NP | No Grade ≥3 NP | Hazard ratio/Odds ratio | p value |
|---|---|---|---|---|---|
| ITT population (n = 1200) | OS, months (mo) | 15.1 | 12.4 | 0.78 | 0.0002 |
| PFS, mo | 3.7 | 2.8 | 0.79 | 0.0001 | |
| PSArr, % n = 1079 | 44.1 | 25.5 | 2.3 | <0.0001 | |
| C25 (n = 602) | OS, mo | 15.3 | 12.2 | 0.77 | 0.009 |
| PFS, mo | 3.5 | 3.5 | 0.84 | 0.07 | |
| PSArr, % n = 538 | 46.2 | 34.5 | 1.6 | 0.015 | |
| C20 (n = 598) | OS, mo | 14.6 | 12.6 | 0.78 | 0.006 |
| PFS, mo | 4.2 | 2.3 | 0.75 | 0.0008 | |
| PSArr, % n = 541 | 40.7 | 21.3 | 2.5 | <0.0001 | |
| Neutrophilia (n = 174) | OS, mo | 12.8 | 7.5 | 0.63 | 0.004 |
| PFS, mo | 4.1 | 2.1 | 0.66 | 0.008 | |
| PSArr, % n = 156 | 43.8 | 16.9 | 3.8 | 0.0002 |
Conclusions
Post hoc assessment of Grade ≥3 NP in PROSELICA was associated with improved survival and response to cabazitaxel independent of dose. These results are consistent with data obtained in the Phase 3 TAX327 (docetaxel) and TROPIC (cabazitaxel) trials. Funded by Sanofi.
Clinical trial identification
NCT01308580.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Editorial Acknowledgement
Editorial assistance was provided by Danielle Lindley of Meditech Media Ltd, funded by Sanofi.
Disclosure
Meisel: Advisor: Astellas, Roche, Celgene, Novartis, Vifor, Sanofi, Amgen, Merck; Expert testimony: Sanofi; Research funding: Bayer (himself), Merck (institution); Expenses: Amgen, Astellas, Sanofi, Servier, Roche, Boehringer Ingelheim; Intellectual property: Merck. R. de Wit: Consultancy, Speaker fees: Sanofi. S. Oudard: Consultancy, Advisory role, Honoraria, Expense: Sanofi, Astellas, Janssen, and Ipson; Research funding: Sanofi; Speakers bureau: Sanofi, Janssen. O. Sartor: Advisor: Bellicum Pharmaceuticals, Dendreon; Advisor, Expenses: Bayer, Johnson & Johnson, Medivation, Oncogenex, Sanofi, Tokai Pharmaceuticals, AstraZeneca, Progenics; Funding (Institute): Bayer, Johnson & Johnson, Sanofi, Dendreon, Endocyte, Innocrin Pharma, Progenics. F. Stenner-Liewen: Consultancy, Advisory role, Research, expenses: Sanofi. S. Guillonneau, A. Ozatilgan: Employee: Sanofi. M. Eisenberger: Honoraria, Consultancy, Advisory role: Sanofi, Pfizer, Astellas; Research: Sanofi; Expenses: Sanofi, Pfizer. J.S. de Bono: Honoraria: Sanofi; Advisor: Sanofi, AstraZeneca, GSK, Genentech, Roche, Merck; Speakers bureau: AstraZeneca/MedImmune; Research funding (Institute): AstraZeneca/MedImmune, GSK, Sanofi, Merck Sharp & Dohme, Genmab, Genentech; Patent on abiraterone acetate with prednisone.
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