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 NET with/without adjuvant chemotherapy (CT). We presented the first report about the relationship between DFS and clinical response to NET at median follow-up 4Y in SABCS 2017. We now present new data corrected according to long follow-up (median 5.9Y).
Postmenopausal BC pts with ER +/HER2 negative, T1c-2, clinically node negative, and under 76 years old were enrolled at primary registration. Pts were treated by leterozole (LET) in weeks 24-28 after primary enrollment. Pts who experienced progression of disease (PD) during neoadjuvant phase were excluded at randomization and received systemic therapy driven by investigators before or after surgery. Pts who met eligibility criteria were randomized 1:1 to LET for 4.5-5 years after CT or LET alone for 4.5-5 years without CT after surgery. DFS/OS in patients showing CR, PR, SD or PD response to NET are secondary endpoints and DDFS is an exploratory endpoint.
Between May 2008 and June 2013, 904 patients were enrolled at primary registration from 100 institutions in Japan and 21 pts were withdrawn during neoadjuvant phase. The median age was 63 years, T1c: 36%, T2: 64%, and progesterone receptor (PgR) +: 79%. Clinical response rates (CR, PR, SD and PD) were 2% (16pts), 48% (421pts), 46% (403pts) and 5% (43pts), respectively. In each response, 0% (0/16), 10.7% (45/421), 12.7% (51/403), and 44.2% (19/43) experienced DFS events and 0% (0/16), 5.2% (22/421), 7.2% (29/403) and 26% (11/43) experienced DDFS events. DDFS in PD pts to NET were statistically significantly worse than CR, PR, SD pts (p < 0.001, hazard ratio 4.83 (95% CI:2.52-9.29). The predictive markers of PD for NET were PgR status (P < 0.001) and Ki67 status (P = 0.041) in biopsy specimen among factors evaluated by multivariate analysis
The DDFS of PBC pts excluding PD pts to NET is excellent regardless of treatment with/without CT. NET with utilization of PD response as a prognostic marker can be considered as a standard treatment option for these patients.
Clinical trial identification
Legal entity responsible for the study
The parent NEOS study was sponsored by CSPOR (Comprehensive Support Project for Oncology Research), part of a Sponsored by CSPOR and Novartis and Chugai Pharmaceuticals provided funding to CSPOR.
H. Iwata: Research: Chugai, Novartis, MSD, Lilly; Honororia: Chugai, AstraZeneca, Daiichi Sankyo; Advisory Board: Daiichi Sankyo, Chugai, Lilly, Kyowa Hakko Kirin, Pfizer, Novartis, AstraZeneca. N. Masuda: Honoraria: Chugai, AstraZeneca, Pfizer, Takeda; Research: Chugai, Novartis, MSD, Eli-Lilly, AstraZeneca, Daiichi Sankyo, Kyowa- Kirin, Pfizer. T. Toyama: Research fund: Eisai, Kyowa Kirin, Takeda, Chugai, Novartis, Nippon Kayaku, Pfizer, Daiichi Sankyo; Advisory board: AstraZeneca. M. Kashiwaba: Honoraria: Chugai, AstraZeneca. Y. Ohashi: Honororia: Chugai, PHRF; Consultant: Chugai; Research fund: Eisai. All other authors have declared no conflicts of interest.