ATLANTAIn 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-As 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
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 dont 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.