Abiraterone acetate plus prednisone/prednisolone (AAP) is licenced in the EU for use in “high risk” newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) based on results of the LATITUDE trial. However, the STAMPEDE “AAP comparison” did not suggest a differential effect, with similar benefits in M0 & M1 patients (pts). We evaluate heterogeneity of AAP effect on overall (OS) & failure-free-survival (FFS) in pts with LATITUDE defined high & low risk M1 disease treated with androgen deprivation therapy (ADT) or ADT + AAP, randomised within the STAMPEDE trial.
Staging scans were evaluated centrally for M1 pts randomized to ADT (Arm A) or AAP (Arm G) within trial. Following review, pts were classified as low or high risk according to the LATITUDE criteria. The primary study endpoint was overall survival (OS) & the secondary endpoint was failure-free survival (FFS). Further exploratory analysis evaluated skeletal related events (SRE), progression free survival (PFS) & prostate cancer specific survival (PCSS). Secondary differential analysis by tumor volume (high/low) was done using the criteria defined in CHAARTED.
901 of 990 eligible M1 pts were evaluable. Median age 67yr, median PSA 96ng/ml, median follow up 42mth. 473 pts were high risk & 428 low risk according to LATITUDE criteria. AAP treated pts had clinically & statistically significant OS improvements in both high (HR: 0.54, 95% CI [0.41-0.70]; p<0.001) & low (HR: 0.66, 95% CI [0.44-0.98]; p=0.041) risk groups. Pts receiving AAP also benefited from prolonged FFS within both high (HR: 0.31, 95% CI [0.25-0.39]; p<0.001) & low risk groups (HR: 0.238, 95% CI [0.17-0.33]; p<0.001). No evidence of heterogeneity between risk groups was found in OS or FFS (interaction p-value, p=0.385 & p=0.294 respectively). Further analyses incorporating the alternative CHAARTED volume definition was done with similar outcomes.
Men with primary mHSPC treated with AAP plus ADT had a significant increase in OS & FFS compared to those receiving ADT alone, irrespective of risk/volume sub-classification. These results show AAP treatment benefit across all mHSPC pts, irrespective of M1 risk/volume sub-stratification using conventional imaging.
Clinical trial identification