Abstract 1371P
Background
ADT + DOC became a standard of care in MHSPC. CHAARTED and STAMPEDE clinical trials incorporated 6 cycles of DOC for induction along with ADT, while GETUG-AFU-15 used 9 cycles of DOC. It was hypothesized that earlier use of DOC in relation to ADT initiation was better. A meta-analysis of individual patient (pt) data from CHAARTED and GETUG-AFU-15 data was performed.
Methods
Data were collected from NCI (CHAARTED) and the UNICANCER (GETUG) after execution of data transfer agreements. We stratified the group using burden (high/ HV vs low volume/ LV) and prior local definitive treatment (PLT) (Y vs N) and analyzed outcomes by start of DOC < 35 days (d) or ≥35 d of randomization. We included pts from both trials who were treated with ADT + DOC. A Cox proportional hazards model, stratified by protocol, was used to examine these three factors, adjusted for age, on OS in both univariate and multivariate models. Median OS was calculated using the Kaplan-Meir method.
Results
ECOG 3805/GETUG meta-analysis was conducted for potential relation of time to docetaxel, volume of disease and prior local therapy to outcomes. There were 332 pts who initiated DOC <35 d ADT and 319 who initiated it ≥ 35 d (CHAARTED, n=470 and GETUG, n=181). Univariate analysis showed shorter time to DOC, LV and PLT were significant in predicting longer OS. Multivariate analysis showed HV pts who had PLT (HVY) had a longer OS compared to HV pts who did not have PLT (HVN)(p=0.015). Time to DOC in days was associated with prior local treatment (p<0.001) and with tumor volume (p=0.06). Average number of days to DOC was lower in the group of pts who had PLT both in HV as well as LV category (HV 31.6 vs LV 25.5 days) when compared to no local treatment group (HV 44.6 vs LV 40.3 days). Table: 1371P
Overall survival
| Variables | Univariate | Multivariate analysis |
| Age | HR=1.024 95% CI (1.003, 1.045) | HR=1.028 95% CI (1.008, 1.049) |
| Time to DOC <35 days (ref) vs ≥35 days | HR=1.442 95% CI (1.113, 1.868) | HR=1.056 95% CI (0.737 1.514) |
| HV vs LV (ref) | HR=2.408 95% CI (1.796, 3.230) | HR=2.212 95% CI (1.372, 3.566) |
| Local treatment vs no local treatment (ref) | HR=2.404 95% CI (1.714, 3.372) | HR=2.844 95% CI (1.679, 4.820) |
| HVY (n=74) | Median OS=71.4 months 95% CI (49.2, >71.4) | |
| HVN (n=331) | Median OS=40.5 months 95% CI (36.8, 49.4) | |
| LVY (n=106) | Median OS>109 months 95% CI (75.0, >109) | |
| LVN (n=140) | Median OS=69.7 months 95% CI (59.6, >69.7) |
CI=Confidence interval
Conclusions
This meta-analysis suggests OS benefit from PLT and lower volume of disease in MHSPC pts treated by ADT + DOC. After accounting for known major prognostic factors, earlier use of DOC was not associated with better survival.
Clinical trial identification
NCT00309985, NCT00104715.
Editorial acknowledgement
Legal entity responsible for the study
NCI, NCTN and UNICANCER.
Funding
Has not received any funding.
Disclosure
S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, Pfizer, Exelixis, Corvus, Sanofi/ Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Calithera, Corvus, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: AAA, Alliance Merck-Pfizer, Astellas, BMS, Janssen, Pfizer, Ipsen, Alliance Merck-Pfizer; Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Sanofi, Ipsen, AstraZeneca, BMS; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. C.J. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech, Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. All other authors have declared no conflicts of interest.