Combined Analysis of Trials of Timing of Androgen Deprivation Therapy after RT

Chicago—Results of the TOAD trial demonstrated that in progressive or relapsed prostate cancer patients after radical radiotherapy (RT) or prostatectomy plus RT, overall survival was improved with immediate androgen deprivation therapy (ADT) compared with delayed ADT. Time to clinical progression was also improved in that patient population with immediate versus delayed ADT. ELAAT (NCT00439751) was a similarly designed trial that failed to reach its accrual goal. Prior to activation of ELAAT, the two investigative teams planned a combined analysis.

Andrew Loblaw, MD, and colleagues presented the planned combined analysis of the two randomized phase 3 trials during a poster session at the ASCO 2018 Annual Meeting. The poster was titled Timing of Androgen Deprivation Therapy for Prostate Cancer Patients after Radiation: Planned Combined Analysis of Two Randomized Phase 3 Trials.

The prostate-specific antigen (PSA) failures for the TOAD trial and 78 of 79 patients accrued to ELAAT were combined. (One patient was excluded due to development of castration-resistant prostate cancer [CRPC].) Both trials randomized participants in a 1:1 ratio to immediate ADT or delayed ADT. The main end point of interest was all-cause mortality by intention-to-treat. Secondary end points included cancer-specific mortality, local progression, distant progression, CRPC, and complications related to prostate cancer.

A total of 261 patients from TOAD and 78 from ELAAT were followed for a median of 5.0 years. Patients in the TOAD trial were younger (mean age, 70.5 vs 73.8 years) and  had more relapse-free interval <2 years from RT (30% vs 10%). In the delayed ADT arms, 63% received ADT a median of 1.58 years for TOAD, and 38% a median of 1.65 years for ELAAT. Mean pre-ADT PSAs were 3.52 and 30.2 ng/mL in the immediate ADT and delayed ADT arms of TOAD, and 3.98 and 18.1 ng/mL in ELAAT, respectively.

There were 60 deaths among TOAD participants and 20 among ELAAT participants. There were no statistical differences between the immediate ADT and delayed ADT arms in all-cause mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.40-1.41; P=.37) and cancer-specific mortality (HR, 0.57; 95% CI, 0.22-1.49).

In the immediate ADT arm, time to local progression (survival time ratio, 1.97; 95% CI, 1.28-3.04; P=.002) was higher as was time to distant progression (survival time ratio, 1.28; 95% CI, 1.04-1.58; P=.02), while prostate cancer-related complication rate was lower.

“No difference in overall survival was detected between immediate ADT and delayed ADT in the combined analysis. A possible explanation is that ELAAT accrued older patients with lower risk of cancer-specific mortality and had a smaller difference in PSA between the immediate ADT and delayed ADT arms,” the researchers said.

Source: Loblaw A, Bassett J, D’Este C, et al. Timing of androgen deprivation therapy for prostate cancer patients after radiation: Planned combined analysis of two randomized phase 3 trials. Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.