Double blind phase III trial of placebo (P) vs. megestrol acetate (MA) 20 mg vs. MA 40 mg as treatment for symptoms of ovarian failure in breast cancer survivors: Initial results of Southwest Oncology Group S9626

Progestins such as MA have been shown lo reduce vasomotor flashes (VF) in breast cancer survivors with ovarian failure. Previous studies were of very short duration and tested a single MA dose. Therefore, S9626 was designed to determine optimal MA dose and duration of benefit in patients with VF refractory to non-hormonal therapy. Methods: Women with T1-3N0-1M0 breast cancer were eligible after completion of surgery and chemotherapy if they had ≥ 10 VF of any severity or ≥5 severe VF/wk. Ongoing tamoxifen (tam) was allowed if started ≥4 months prior to registration. Double blind randomization was to P, MA 20 mg or MA 40 mg for 3 months (strata: tam use, number VF, duration VF). Success at 3 months was defined as ≥75% reduction in VF. If success, another 3 months of blinded drug was given; if not, open label MA 20 mg was added to blinded drug and continued for 3 months. The trial concluded at the 6 month VF assessment. Further treatment was at investigator discretion. Assessments of toxicity, weight, and patient-reported quality of life (QOL) including mood, vaginal dryness, and sexual function were obtained at baseline, 3, and 6 months. Results: 288 women were randomized, of whom 15% were on tam, 40% had over 63 VF/week, and 74% had VF for ≥6 months. Success at 3 months was 14% P, 67% MA 20 mg and 48% MA 40 mg (chi square, 2df p<.0001). Most successes at 3 months continued at 6 months (64% P, 74% MA 20 mg, 82% MA 40 mg). Weight gain was reported in 11% P, 4% MA 20 mg and 8% MA 40 mg; depression: 8%, 5%, 13%; fatigue: 8%, 6%, 13%. Data on benefit from adding open label MA 20 mg at 3 months will be available in 12/01, as will QOL endpoints. Conclusions: Randomized symptom management studies in breast cancer survivors are feasible in cooperative group settings. MA significantly reduced VF with durable benefit over 6 months. 20 mg/d may be the preferred dose.