Meta-analysis Shows Benefit of LHRH-A Plus Tamoxifen in Advanced Breast Cancer Therapy

ATLANTA—In a meta-analysis of four trials of premenopausal women with advanced breast cancer, the combination of an LHRH-agonist (LHRH-A) and tamoxifen (Nolvadex) was clearly more effective than an LHRH-A alone, according to a presentation at the 35th Annual Meeting of the American Society of Clinical Oncology.

“All of the trials addressed the issue of possible superiority of so-called complete estrogen deprivation vs gonadal ablation alone,” said Francesco Boccardo, MD, of the National Tumor Institute and University of Genoa, Italy, on behalf of the Combined Hormonal Agents Trialists (CHAT) Group.

Individual patient data were collected for 506 patients from the four trials. Three trials involved goserelin (Zoladex)—the Zeneca 2302 international trial (318 patients), an Italian trial (48 patients), and a Japanese trial (33 patients). The fourth study used buserelin (EORTC 10881, 107 patients).

Overall, 79% of patients were treated with goserelin (3.6 mg every 4 weeks) as the LHRH-A , and 21% received buserelin (6.6 mg every 6 weeks for 12 weeks, then every 8 weeks). All LHRH-A’s were administered as subcutaneous depots. Tamoxifen was given at 40 mg/d in the EORTC and international trials, 30 mg/d in the Italian trial, and 20 mg/d in the Japanese trial.

Dr. Boccardo reported that the primary endpoint of the comparison was overall survival with stratification for estrogen-receptor status, disease-free interval, and dominant site of disease. Secondary endpoints were progression-free survival, response rate, and duration of response.

The LHRH-A plus tamoxifen combination showed significant improvement over LHRH-A alone with respect to all efficacy endpoints, he said. Median overall survival was 2.9 years with the combination vs 2.5 years with tamoxifen alone (P = .02); median progression-free survival was 8.7 months vs 5.4 months (P < .001); response rate was 39% vs 30% (P = .03); and median duration of response was 19.4 months vs 11.3 months.

Subgroup analyses for estrogen-receptor status, disease-free interval, and dominant site of disease all showed trends in favor of the combination, he said.

 “I don’t believe that it is mandatory on the basis of these data to use castration in combination with tamoxifen, but it is my opinion that the data provide sound evidence for this combined treatment as a reasonable choice for these women,” Dr. Boccardo said. He said also that the data provide a rationale for the use of complete estrogen deprivation in women with early-stage breast cancer in the adjuvant setting.