6-month androgen deprivation therapy fails to show non-inferior survival

Prolonged androgen suppression resulted in a 5-year overall survival of 85.3% with prolonged androgen deprivation therapy versus 80.6% for the abbreviated course, investigators in a multicenter European trial reported at the 2007 American Society of Clinical Oncology annual meeting here. The difference translated to a mortality hazard ratio of 1.43 (96.4% CI: 1.04-1.98) for 6 months' hormonal treatment, which did not meet the trial's definition of non-inferiority.

More than a decade ago, Dr. Bolla and colleagues in the European Organization for Research and Treatment of Cancer (EORTC) established 3 years of adjuvant hormonal treatment as the standard of care for patients with locally advanced prostate cancer (N Engl J Med 1997; 337:295-300). Whether an abbreviated course of androgen deprivation would work just as well had not been determined.

EORTC investigators randomized 1,117 patients with locally advanced prostate cancer to 6 months or 36 months of post-irradiation androgen deprivation therapy. The primary objective was to demonstrate the non-inferiority of short-course adjuvant therapy compared to standard treatment. Non-inferiority was defined as a mortality hazard ratio of ≤1.35 for abbreviated androgen deprivation versus standard therapy.

All patients received a 70-Gy total dose of radiation in the form of external beam radiation therapy, followed by 6 months of combined androgen ablation. The patients were then randomized to no further hormonal treatment or to 30 months of additional androgen deprivation with a leuteinizing hormone-releasing hormone agonist.

Dr. Bolla reported that 147 patients did not receive randomized therapy, primarily because of toxicity (19.7%) and patient refusal (38.1%). That left 970 patients available for outcome analysis.

The trial was stopped early after a planned interim analysis suggested futility for the comparison and a clear advantage for prolonged androgen deprivation. After a median follow-up of 5.2 months, the short course of adjuvant androgen deprivation was associated with a mortality of 20.7% versus 15.0% among patients treated for 36 months. The resulting mortality hazard ratio of 1.43 failed to meet the pre-specified non-inferiority definition of ≤1.35.

When the trial was stopped, clinical progression-free survival was 81.8% with prolonged adjuvant therapy and 69% with abbreviated treatment (p<.0001). Biochemical progression-free survival was 78.27% among patients who received 3 years of adjuvant therapy versus 58.93% in those who received only 6 months of hormonal treatment (p<.0001). Assessment of global health status/quality of life demonstrated no difference between the treatment groups.