LAUSR

Aims We investigated the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane (EXE) alone followed by subsequent tailored treatment with EXE alone for responders or EXE plus oral metronomic cyclophosphamide (CPA) for non-responders. Methods In this multicenter open-label phase II study, we enrolled postmenopausal patients with primary invasive estrogen receptor (ER)-positive, HER2-negative, stage I–IIIA (T1c–T3 N0–2 M0) breast cancer and Ki67 index ≤ 30%. Patients first received EXE 25mg/day for 12 weeks. Based on clinical response and change in Ki67 index in response to the initial therapy, patients who achieved complete response (CR), partial response (PR) with Ki67 index ≤5% after treatment, or stable disease (SD) with Ki67 index ≤5% both before and after treatment were defined as responders. Non-responders were defined as patients with PR and Ki67 index >5% after treatment, or SD and Ki67 index >5% before or after treatment. For the subsequent 24 weeks, responders continued the EXE monotherapy (continued EXE group), whereas non-responders switched to combination therapy with EXE plus CPA 50mg/day (EXE+CPA group). The primary endpoint was clinical response (CR and PR) at weeks 24 and 36. Results A total of 59 patients (median age 69 years, range 53–86 years) were enrolled between January 2011 and July 2015. After exclusion of 3 (2 with progressive disease, 1 with an adverse event, AE) who discontinued treatment in the initial 12-week EXE monotherapy period, 56 remained enrolled to receive subsequent treatment. After 8–12 weeks of the initial EXE monotherapy, 14 patients were classified as responders (9 with PR and Ki67 index ≤5% after treatment; 5 with SD and Ki67 index ≤5% before and after treatment), whereas 42 were classified as non-responders (3 with PR and Ki67 index >5% after treatment; 39 with SD and Ki67 index >5% before or after treatment). Clinical response rates at weeks 24 and 36 were 85% (12/14, 95%CI 57.2–98.2%) and 76% (10/13, 95%CI 46.2–95.0%), respectively, in the continued EXE group, and 56% (23/41, 95%CI 39.7–71.5%) and 76% (30/39, 95%CI 60.7–88.9%), respectively, in the EXE+CPA group. At week 36, no significant difference was found in median Ki67 index between the continued EXE and EXE+CPA groups (3.5% and 4.0%, respectively). The proportion of patients with preoperative endocrine prognostic index (PEPI) 0 was also similar between the continued EXE and EXE+CPA groups (21.4% and 23.8%, respectively). The breast-conserving surgery rate was 71.4% and 69.0%, respectively. Grade 3 AEs were elevated liver enzymes (1 patient) in the continued EXE group, and gastritis, hypertriglyceridemia, and bone mineral density loss (1 patient each) in the EXE+CPA group. Conclusion Switching from EXE monotherapy to EXE+CPA combination therapy based on clinical response and biological response (change in Ki67 index) to initial therapy improved subsequent clinical response in non-responders. Favorable clinical response to EXE alone was maintained in responders. Tailored neoadjuvant endocrine and chemo-endocrine therapy was shown to be effective in postmenopausal ER-positive breast cancer patients. (JBCRG-11CPA; UMIN000004751) Citation Format: Masuda N, Sato N, Morimoto T, Ueno T, Kanbayashi C, Kaneko K, Yasojima H, Saji S, Sasano H, Morita S, Ohno S, Toi M. Tailored neoadjuvant endocrine and chemo-endocrine therapy for postmenopausal patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-13-06.