(ChemotherapyAdvisor) — Intermittent androgen deprivation (IAD) was noninferior to continuous androgen deprivation (CAD) in men with hormone-sensitive metastatic prostate cancer. In men with minimal disease, however, IAD was statistically inferior, “suggesting that CAD is the preferred treatment in this group,” according to results of a long-awaited international phase 3 trial reported at the 2012 American Society of Clinical Oncology Annual Meeting.
Preclinically, IAD prolonged time to castration resistance, and early clinical data indicated feasibility and potential for better quality of life in patients for whom median survival is 2.5 years, said Maha Hussain, MD, of the University of Michigan, Ann Arbor, on behalf of the trial investigators in explaining the study’s rationale.
“Some doctors recommend intermittent hormonal therapy to men with metastatic prostate cancer, believing it will reduce their risk of side effects without compromising their outcome, but these findings demonstrate a clear downside to this approach for certain men,” said Dr. Hussain. “The findings clearly demonstrate that intermittent hormonal therapy is not safe for all patients with metastatic prostate cancer. They will be practice-changing for many doctors in the U.S. and abroad who routinely use intermittent therapy.”
In this National Cancer Institute-sponsored intergroup study, 3,040 patients with hormone-sensitive metastatic prostate cancer were accrued by the Southwest Oncology Group, the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, the National Cancer Institute of Cancer, and the European Organization for Research and Treatment of Cancer between May 1995 and September 2008. Performance status (PS) was 0-2.
Those patients with PSA ≥5ng/mL were treated with 7 months of goserelin plus bicalutamide. Those achieving a PSA ≤4 ng/mL in months 6 and 7 were stratified by prior neoadjuvant androgen deprivation/finasteride, PS, disease extent (minimal or extensive) and then randomized to CAD or IAD. The primary objective was to assess if overall survival (OS) with IAD was noninferior compared to CAD.
After 7 months of CAD, 1,535 eligible patients achieved PSA ≤4.0. Median age was 70 years, 4% were PS 2, 48% had extensive disease, and 12% had prior neoadjuvant androgen deprivation. All were randomized to CAD (n=759) or IAD (n=770). Median follow-up was 9.2 years.
Median survival for all eligible patients from study entry was 3.6 years and 10-year OS was 17%, the investigators reported. From randomization, median survival was 5.8 years and OS was 29%, in the CAD arm vs 5.1 years and 23% in the IAD arm (HR, IAD/CAD 1.09).
Median OS in men with minimal disease spread (no spread beyond the spine, pelvis, and lymph nodes) was 7.1 years for those who received CAD vs 5.2 years for those who received IAD (HR 1.23; P=0.034). Among men with more extensive disease spread, median OS was similar in both arms (4.4 years for CAD vs 5 years for the IAD arms; HR 0.96; P=0.64).
In the IAD group, 30.3% of patients had grade 3 or 4 related adverse events vs 32.6% in the CAD arm. Prostate cancer was the cause of death in 56% of patients in the CAD arm and 64% in the IAD arm. OS did not differ by race (P=0.44).
“These observations suggest inherent biological differences and warrant further mechanistic evaluation,” Dr. Hussain said.