An open label, randomized phase II trial of primary systemic therapy with exemestane (EXE 25 mg/d) plus epirubicin (EPI, 20 vs 30 mg/m2 q1w × 8–12) in breast cancer: An interim analysis of the German Neoadjuvant Aromasin Initiative (GENARI-3)

Abstract

826 Background: This randomized phase II trial explores the efficacy of EXE, a steroidal aromatase inactivator, in combination with lower doses of EPI, a topoisomerase-II targeted anthracycline, as an alternative presurgical therapy (PST) option for women who may not be eligible for more toxic primary chemotherapy regimens. Methods: Age: ≥ 50 years, postmenopausal hormone receptor (HR) + /−, primary tumors T2, 3, 4a-c, Nx, M0, ECOG PS 0–2. All patients (pts) obtained continuous EXE and were randomized to either 20 mg/m2 (A) or 30 mg/m2 (B) EPI q1w × 8–12. Endpoints (1st/2nd): pathological complete remissions (pCR), rate of breast conserving surgery (BCS), and grade/frequency of toxicity. Results: A total of 23 pts (12 in arm A, 11 in B) with median age of 68 (53–77) and tumor status T2 were enrolled. 28 patients are still under therapy and will be applicable for final analysis at the time of this presentation. All pts were HR+ and were evaluable for toxicity. Four patients (n=3: 20 mg/m2; n=1: 30 mg/m2) had reduced numbers of cycles [5(n=2), 6(n=1), 11(n=1)] after dose delay due to grade (G) 2 toxicity (NCI-CTC): leukopenia (n=2), infection (n=2) or G 3 toxicity: infection (n=1). One patient withdrew consent for pre-operative staging and surgery (arm B, no DLT). Efficacy (22 pts): Clinical responses were as follows: (A/B): clinical partial responses, n= 9/7; clinical stable disease, n= 3/3. Pathological tumor response (A/B): ypT0 (pCR), n=0/1, ypT1a, n=1/0; ypT1c, n=6/2; ypT2, n=4/5; ypT3, n=1/2. BCS: n=19/3. Conclusions: The interim results for 23 of 60 patients suggest good therapeutic efficacy and excellent tolerability of combined EXE and EPI . It has to be shown wether this treatment offers additional benefit for women with hormone- receptor positive breast cancer, who showed lower response to primary chemotherapy when compared to receptor- negative patients. In addition this supports the concept of combination PST as an alternative to hormonal PST in postmenopausal patients. No significant financial relationships to disclose.