Gillian M. Duchesne, MD, of the Peter MacCallum Cancer Centre, Australia, presented the results of the TOAD trial at the Genitourinary (Prostate) Cancer Oral Abstract Session on Sunday, May 31 (Abstract 5007). This randomized, prospective phase III trial was conducted to determine if immediate intervention with androgen deprivation therapy (ADT) would improve overall survival (OS) compared with delayed ADT.
Dr. Gillian M. Duchesne
The analysis combined two groups of patients with prostate cancer enrolled in separate studies: those with prostate-specific antigen relapse after undergoing curative therapy and those who were asymptomatic at diagnosis and not appropriate candidates for curative therapy. All patients were randomly assigned 1:1 to delayed or immediate ADT. The primary endpoint was OS.
The target accrual was 750 patients, but the study enrolled slowly. Results presented were based on 293 patients, 151 receiving delayed ADT and 142 receiving immediate ADT. In the delayed arm, 89 patients (58.9%) received ADT and 61 (40.4%) did not start treatment during the study. The median time to initiation was 18.7 months. Median follow-up was 5.0 years.
Thirty patients died in the delayed arm and 16 in the immediate arm. The immediate-treatment group had better OS compared with the delayed-treatment group (Cox-unadjusted hazard ratio [HR] 0.55, 95% CI [0.30, 1.00]; p = 0.05). Cox-adjusted regression analysis indicated an HR of 0.54 (95% CI [0.27, 1.06]; p = 0.074). Prostate cancer deaths were lower with immediate treatment compared with delayed treatment (6 vs. 12; p = 0.26), as were other causes of death (10 vs. 18; p value not reported). A post hoc analysis of OS found that intermittent ADT was better than continuous ADT in the immediate arm (adjusted HR 0.46, 95% CI [0.20, 1.04]; p = 0.06), but not in the delayed arm (adjusted HR 1.01, 95% CI [0.48, 2.10]; p = 0.98).
Statistically significant delays in time to first local progression (adjusted HR 0.51, 95% CI [0.34, 0.76]; p = 0.001) and time to first metastatic disease (adjusted HR 0.54, 95% CI [0.32, 0.90]; p = 0.018) were seen with immediate treatment. No statistically significant differences were seen for time to castration resistance or time to first prostate cancer complication. In the immediate arm, 77.9% of patients reported symptoms related to ADT therapy compared with 47.3% in the delayed arm.
“As this is not a curative approach, we must be mindful of morbidity,” Dr. Duchesne said. “I think we probably have enough evidence to discuss this with our patients and give them the opportunity of an informed choice.”
Discussant Celestia S. Higano, MD, FACP, of the University of Washington Fred Hutchinson Cancer Research Center, said that this is not the first randomized trial comparing immediate and delayed ADT to fall short of its accrual goal. “I think the trends in the TOAD trial do look provocative,” Dr. Higano said. “[But] they lack the statistical power due to short follow-up, too few events, and the hazard ratio does remain unstable.”
Watch the session: Visit the ASCO Virtual Meeting website.