Abstract 5478
Background
Statins have been shown to block DHEAS uptake by prostate cancer cells by competitively binding to SLCO2B1, an organic anionic intracellular transporter. Use of statins by prostate cancer pts has been associated with longer time to progression (TTP) during ADT in the hormone-sensitive setting (Harshman, JAMA Oncol 2015).
Methods
We evaluated the impact of statin use in PFS and OS in mCRPC patients treated with cabazitaxel or mitoxantrone in the TROPIC phase III trial. Kaplan-Meier, univariable (UV) and multivariable (MV) cox-regression models were constructed to evaluate the association between use of statins and overall survival (OS), PSA progression-free survival (PSA-PFS) and radiographic PFS (rPFS). Covariates included in the multivariable model are listed in the table.
Results
755 pts were included in the analysis. 138 (18.6%) pts received statins: atorvastatin (53 pts, 38.4%), simvastatin (56 pts, 40.6%), rosuvastatin (14 pts, 10.1%), pravastatin (9 pts, 6.5%), lovastatin (4 pts, 2.9%) and fluvastatin (2 pts; 1.4%). 72 pts (52.2%) were allocated to the mitoxantrone arm and 66 pts (47.8%) to the cabazitaxel arm of the trial. Statin use was associated with longer median OS (15.8 vs 13.4m; HR: 0.74; p = 0.01) but no difference in PSA-PFS (4.8 vs 4.6m; HR: 0.98; p = 0.824) or rPFS (8.3 vs 7.2m; HR: 0.94; p = 0.661) was observed. Statin use was associated with a longer time on prior hormone-therapy (5.3 vs 3.7 yrs; p < 0.001). In MV cox-regression models, the impact of statin use in survival was independent of treatment arm (cabazitaxel vs mitoxantrone) and other prognostic factors (Table).Table: 809P
Multivariable Cox-Regression OS Analysis
| Variable | HR (95%CI) | p-value |
|---|---|---|
| Statin Use | 0.79 (0.62-0.99) | 0.048 |
| Treatment Arm | 0.66 (0.55-0.79) | < 0.001 |
| Baseline PSA | 1 (1-1) | 0.394 |
| Baseline Hb | 0.89 (0.85-0.93) | < 0.001 |
| Baseline ALP | 1 (1-1) | 0.009 |
| Visceral Metastases | 1.36 (1.11-1.68) | 0.003 |
| ECOG PS | 1.67 (1.43-1.96) | < 0.001 |
Conclusions
Use of statins by pts treated in the TROPIC trial was associated with a longer OS, independent of treatment arm and other prognostic variables. Further analyses will elucidate the role of statins in mCRPC.
Clinical trial identification
EudraCT: 2006-003087-59; NCT00417079.
Legal entity responsible for the study
David Lorente / Prostate Targeted Therapy Group.
Funding
The TROPIC trial was funded by Sanofi Aventis. No specific funding was received for the development of the current abstract.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.
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