Outcomes of Japanese breast cancer patients treated with pre-operative and post-operative anastrozole or tamoxifen

Abstract

The present study examined long-term efficacy outcomes in a subgroup of postmenopausal, estrogen receptor-positive Japanese breast cancer patients from the Pre-Operative "Arimidex" Compared with Tamoxifen trial, following pre-operative (3 months) and post-operative (5 years) adjuvant treatment with either anastrozole or tamoxifen. Patients with large, potentially operable, locally-advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre-operatively. After surgery at 3 months, patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence, intolerable toxicity or withdrawal of patient consent. Recurrence-free survival and overall survival were measured from the date of randomization to the date of recurrence or death, whichever occurred first. Patients were monitored for adverse events throughout the study period and up to 30 days following administration of the last study medication. During post-operative adjuvant therapy, 4/48 (8%) anastrozole and 25/49 (51%) tamoxifen patients experienced recurrence. There was a significant difference in recurrence-free survival between the two groups (hazard ratio 0.14; 95% confidence interval 0.05-0.41; P = 0.0003). There was a significant increase in overall survival with anastrozole (0.21; 0.05-0.96; P = 0.0436) and there were 2/48 (4%) and 10/49 (20%) deaths with anastrozole and tamoxifen, respectively. Most patients responding to pre-operative therapy remained recurrence-free. Sequential pre-operative/post-operative treatment with anastrozole resulted in lower recurrence and death rates, compared with tamoxifen.

Trial registration: ClinicalTrials.gov NCT00232661.

Figure 1

Patient disposition (completion or discontinuation). ^aThe date of surgery was used to define the end of the neoadjuvant period, as detailed in the statistical analysis plan. ^bTwelve patients who received randomized tamoxifen before unblinding opted to switch to receive open‐label anastrozole. No patients who received randomized anastrozole before unblinding opted to switch to receive open‐label tamoxifen.

Figure 2

Kaplan–Meier plot for: (a) recurrence‐free survival (all randomized Japanese patients) and (b) overall survival (all randomized Japanese patients). Recurrence‐free survival is defined as time to first event, where event is either death or recurrence. Overall survival is defined as time to death. Patients who did not recur or die have been censored; tick marks indicated censored patients. CI, confidence interval.