Abstract P3-13-03: NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy
Authors: Iwata H , Masuda N , Fujisawa T , Toyama T , Ohtani S , Yamamoto Y , Kashiwaba M , Taira N , Sakai T , Hasegawa Y , Nakamura R , Akabane H , Shibahara Y , Sasano H , Yamaguchi T , Ohashi Y 
Published: February 2018

Abstract
Background: Whether adjuvant chemotherapy is required for patients (pts) with intermediate-risk endocrine-responsive postmenopausal breast cancer (BC) remains unknown. Sufficient data have not been available about the long-term prognosis of patients with neoadjuvant endocrine therapy (ET). NEOS is a randomized phase III study that assessed the long-term prognosis of estrogen receptor positive (ER+) primary breast cancer (PBC) pts who received neoadjuvant ET with/without adjuvant chemotherapy.
Methods: Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, under 76 years old were enrolled at primary registration. Pts were treated by leterozole (LET) in weeks 24-28 after primary enrollment. Pts experienced progression (PD) during neoadjuvant phase were excluded at randomization and received any systemic therapy driven by investigators before or after surgery. The long-term prognosis was followed in all registered pts including PD pts. Response to neoadjuvant ET was evaluated as complete response (CR), partial response (PR) or stable disease (SD) using calipers, ultrasound and MRI (or CT) at the baseline and end of treatment before surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after chemotherapy or LET alone for 4.5-5 years without chemotherapy after surgery. Pts excluded at second registration were treated any systemic therapies driven by investigators. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), clinical response rate in neoadjuvant phase, pathological response, and breast-conserving surgery rate. The randomization code have been blinded to the investigators.
Results: Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan (median follow-up: 4.0 years) and 24 pts were withdrawn during neoadjuvant phase. The median age was 63 years, T1c:37%, T2:63%, and PgR+:78%. Clinical response rates (CR, PR, SD and PD) were2% (16pts), 48% (421pts), 45% (400pts) and 5% (43pts), respectively and, in each response category, 0% (0/16), 5.5% (23/421), 7.8% (31/400), and 20.9% (9/43) experienced DFS events. DFS in PD pts to neoadjuvant ET were statistically significantly worse than CR, PR, SD pts (p&lt;0.0001, hazard ratio 4.7 (95% CI:2.3-9.5). The prognosis after surgery in 669 randomized pts was good regardless with/without chemotherapy, forty four pts (6.6%) experienced DFS events after surgery. The predictive markers of PD for neoadjuvant ET were yet unclear among evaluated clinical factors.
Conclusion: This is the first report of DFS in the largest neoadjuvant ET trial (NEOS). The DFS of postmenopausal, ER+/HER2-, PBC pts excluding PD pts to neoadjuvant ET is highly good regardless with/without chemotherapy. Neoadjuvant ET with utilization of PD response as a prognostic marker can be considered as a standard treatment option for these patients. Clinical trial information: UMIN000001090.
Citation Format: Iwata H, Masuda N, Fujisawa T, Toyama T, Ohtani S, Yamamoto Y, Kashiwaba M, Taira N, Sakai T, Hasegawa Y, Nakamura R, Akabane H, Shibahara Y, Sasano H, Yamaguchi T, Ohashi Y. NEOS: A randomized, open label, phase 3 trial of adjuvant chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole: First report of long-term outcome and prognostic value of response to neoadjuvant endocrine therapy [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 P3-13-03.