Mehta RS, et al. - Researchers assessed final survival outcomes in postmenopausal patients who were treated with either anastrozole (aromatase inhibitor) or fulvestrant (selective estrogen-receptor down-regulator) plus anastrozole for hormone receptor–positive metastatic breast cancer. These patients were randomly assigned to these treatment arms previously and prolonged progression-free survival and marginally prolonged overall survival was noted in the fulvestrant plus anastrozole treatment arm as first-line therapy. Increased long-term survival was reported in relation to the addition of fulvestrant to anastrozole vs anastrozole alone, despite substantial crossover to fulvestrant following progression during therapy with anastrozole alone. Patients without previous exposure to adjuvant endocrine therapy especially derived benefit from this treatment strategy.

Methods

• Either anastrozole or fulvestrant plus anastrozole was randomly received by patients.
• Based on adjuvant tamoxifen use, randomization was stratified.
• Researchers carried out survival analysis by using two-sided stratified log-rank tests and Cox regression.
• The two groups, both overall and subgroups, were compared with respect to efficacy and safety.

Results

• Overall 707 patients were randomized, data sufficient for analysis was available in 694.
• A total of 247 deaths among 349 women (71%) and a median overall survival of 49.8 months was observed in the combination-therapy group vs anastrozole-alone group had 261 deaths among 345 women (76%) and a median overall survival of 42.0 months, a significant difference (hazard ratio for death, 0.82; 95% confidence interval [CI], 0.69 to 0.98; P=0.03 by the log-rank test).
• Women who had not received tamoxifen previously experienced a longer overall survival with the combination therapy than with anastrozole alone (median, 52.2 months and 40.3 months, respectively; hazard ratio, 0.73; 95% CI, 0.58 to 0.92); the two groups demonstrated similar overall survival among women who had received tamoxifen previously (median, 48.2 months and 43.5 months, respectively; hazard ratio, 0.97; 95% CI, 0.74 to 1.27) (P=0.09 for interaction); these findings were reported in a subgroup analysis of the two strata.
• The two groups had a similar incidence of long-term toxic effects of grade 3 to 5.
• In the anastrozole-alone group, about 45% of the patients crossed over to receive fulvestrant.