HOUSTON--A survival update of two mature phase III trials shows that postmenopausal women with advanced breast cancer who received anastrozole(Drug information on anastrozole) (Arimidex) after failing therapy with tamoxifen(Drug information on tamoxifen) (Nolvadex) survived significantly longer than those given megestrol(Drug information on megestrol) acetate (Megace). In addition, patients treated with anastrozole had fewer side effects.
Aman Buzdar, MD, professor of breast medical oncology, University of Texas M.D. Anderson Cancer Center, and his colleagues reported the survival results, with a median of 31 months of follow-up, in the September 15, 1998, issue of Cancer.
Two Parallel-Group Studies
The two randomized, parallel-group, multicenter studies--a North American study led by Dr. Buzdar and a study from Europe, South Africa, and Australia--were identical in design, allowing the data to be combined for analysis. A total of 764 patients were randomized to receive anastrozole at two different doses, 1 mg daily and 10 mg daily, or megestrol, 40 mg four times daily.
At the time of data cut off, Dr. Buzdar reported, 473 patients had been followed until death--151 in each of the two anastrozole groups and 171 in the megestrol group. The estimated 2-year survival rates from the combined analysis were 56%, 54%, and 46% for patients receiving anastrozole 1 mg/d, anastrozole 10 mg/d, and megestrol, respectively.
Hazard ratios indicated a significant survival benefit for 1 mg anastrozole, compared with megestrol (HR = 0.78), indicating "that patients on anastrozole 1 mg are 22% less likely to die over a given time period than are patients on megestrol acetate," Dr. Buzdar said. The 10-mg anastrozole dose showed a trend toward a survival benefit over megestrol.
Significant Survival Advantage
Both anastrozole 1 mg and 10 mg showed an advantage in estimated median time to death (26.7 and 25.5 months, respectively), compared with megestrol (22.5 months). The anastrozole 1 mg dose provided a significant survival advantage of 4.2 months. "It is likely that the differences between the 1 and 10 mg anas-trozole doses were due to the variability that may be inherent to clinical trials involving advanced breast carcinoma patients," Dr. Buzdar said.
The 12-month safety analysis showed that all three treatments were generally well tolerated. Megestrol was withdrawn from 10 patients because of adverse drug reactions, compared with five patients and seven patients for anastrozole 1 mg and 10 mg, respectively. There were no treatment-related deaths with anastrozole whereas two possible treatment-related deaths occurred with megestrol.
Dyspnea, hypertension, sweating, vaginal hemorrhage, weight gain, and increased appetite were all reported two or more times more often with megestrol than with anastrozole. Transient diarrhea occurred more often with anastrozole.
"These data represent the first reported significant survival advantage for an aromatase inhibitor compared with another endocrine agent," Dr. Buzdar said. "The large size of the trials and the strict response and statistical criteria employed add weight to the significance of this finding," he added.
Studies currently in progress are directly comparing anastrozole with tam-oxifen, both as first-line treatment for advanced disease and as adjuvant treatment for early-stage breast cancer.