Background: Clinical evidence for the anticancer activity of adjuvant zoledronic acid (ZOL) in patients with early stage breast cancer (BC) has been reported in several randomized clinical trials including ZO-FAST, AZURE (>5 yr postmenopausal subset), and ABCSG-12. In addition, combining ZOL with standard neoadjuvant therapy improved pathologic complete response (pCR) and reduced the need for mastectomy in the AZURE trial. The open-label, multicenter, phase 2, FEMZONE trial examined the effect of neoadjuvant letrozole (LET) ± ZOL on tumor response in postmenopausal patients with hormone receptor-positive (HR+) primary BC. Here, we report the efficacy and safety after 6 mo of treatment.
Methods: Postmenopausal women with HR+ BC and ECOG performance status of 0–2 were randomized to LET (2.5 mg/d) ± ZOL (4 mg q4w). The primary efficacy endpoint was objective response rate (ORR; complete + partial response per RECIST criteria) at 6 mo by central review. Secondary endpoints included ORR in the per-protocol and safety populations, best response, breast-conserving surgery, pCR, change in tumor size, overall survival, and safety. Between-group differences in ORR were evaluated using Fisher's exact test.
Results: Among enrolled patients (N = 168; mean age 70.9 yr; mean treatment duration 6.5 mo), patients receiving LET + ZOL experienced numerically better ORR at 6 mo versus LET alone (69.2% vs 54.5%, respectively), with a between-group difference of 14.7% (P = .106). Although the primary endpoint did not reach statistical significance because of insufficient patient recruitment, the prespecified between-group difference of ≥10% was met. A similar trend in ORR at 6 mo favoring ZOL was also seen by local assessment (Δ11%, P = .192). At 4 mo, higher ORR was observed for LET + ZOL versus LET alone both for the local (33.3% vs 24%, respectively) and central assessments (41.5% vs 30.3%, respectively). Numerically more patients receiving LET + ZOL experienced a partial response at 6 mo versus LET alone (66.2% vs 54.5%, respectively). At 6 mo, the mean tumor size had decreased from 3.34 ± 1.98 cm to 2.1 ± 1.76 cm in the overall patient population, and the decrease was slightly larger with LET + ZOL compared with LET alone (–1.37 ± 0.96 cm vs −1.12 ± 0.92 cm, respectively). Overall, there was no difference in the number of patients requiring mastectomy between LET + ZOL and LET alone (15.6% vs 15.2%, respectively). Incidence of adverse events (AEs) was slightly higher among patients receiving LET + ZOL versus LET alone (92.1% vs 81%, respectively), and the types of AEs were consistent with the known safety profiles of these agents. No deaths or osteonecrosis of the jaw was reported during the course of the study.
Conclusions: This study provides additional confirmation of the efficacy of LET as neoadjuvant therapy for early HR+ BC, and supports previous reports of ZOL's anticancer activity in this setting (as evidenced by the trend toward improved ORR with ZOL + LET versus LET alone). These data, together with other published ZOL studies, suggest that adding ZOL to neoadjuvant therapy may be considered for postmenopausal patients scheduled to receive neoadjuvant endocrine therapy for BC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-02.
