Abstract PD07-02: Anticancer activity of letrozole plus zoledronic acid as neoadjuvant therapy for postmenopausal patients with breast cancer: FEMZONE trial results

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-12, Vol.72 (24_Supplement), p.PD07-02-PD07-02
• Main Authors: Fasching, PA, Jud, SM, Hauschild, M, Kümmel, S, Schütte, M, Warm, M, Hanf, V, Muth, M, Baier, M, Schulz-Wendtland, R, Beckmann, MW, Lux, MP
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS12-PD07-02

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