Abstract P4-13-09: Sequential second line endocrine therapy is still an effective strategy for postmenopausal ER+ and HER2- advanced breast cancer with low sensitivity to initial endocrine therapy
Authors: Araki K , Fujisawa T , Sakamaki K , Kikawa Y , Iwamoto T , Sangai T , Shien T , Takao S , Nishimura R , Takahashi M , Aihara T , Mukai H , Taira N 
Published: May 2019

Abstract
Background:It is unclear how to define responsiveness to endocrine therapy (ET) during the clinical course of advanced breast cancer (ABC), especially in evaluation of the effect of sequential ET. Objective:The goal of the study was to evaluate the efficacy of second line treatment of physician's choice (2nd-line TPC) for estrogen receptor-positive (ER+) and HER2-negative postmenopausal ABC with very low or low sensitivity to initial ET. Methods:A multicenter prospective observational cohort study was performed for 2nd-line TPCs. ABC with low sensitivity to initial ET was defined as recurrence within 5 years (yrs) during adjuvant ET or progression within 9 months (mo.) of initial ET. Similarly, ABC with very low sensitivity to initial ET was defined as recurrence within 2 yrs during adjuvant ET or progression within 3 mo. of initial ET. The expected clinical benefit rate (CBR: defined as patients who achieved CR, PR or SD for 24 weeks) was 50%. The null hypothesis of a CBR of 30% was tested with a one-sided α of 5%. 90% confidence intervals (CIs) were calculated for hypothesis tests. Results: A total of 56 patients (pts) were enrolled, but 7 were ineligible and one discontinued before starting the protocol treatment. The median age was 66 yrs (range: 41-88) and the median BMI was 23.4 kg/m2 (16.4-31.9). All pts were ER+ and 80% were PgR+. Most of pts had a baseline PS of 0 or 1, 90% had invasive ductal carcinoma, and 10% had invasive lobular carcinoma. Postoperative recurrence was detected in 84% and these pts had a median duration of adjuvant ET of 30.5 mo. (5.3-58.9). De novo stage IV ABC was present in 16%, with a median duration of first-line ET of 5 mo. (2.3-10.8). Adjuvant chemotherapy including anthracycline- and/or a taxane-containing regimen was administered in 58% (29/49). As adjuvant ET before initial recurrence, 34 pts received non-steroidal aromatase inhibitors (AIs) (88.0%), 1 received a steroidal AI (2.3%), and 3 received a selective estrogen receptor modulator (SERM). As first line ET in de novo stage IV, 7 pts (14%) were treated with AIs or a SERM (1 case). 2nd-line TPCs were also used, with 40 pts receiving fulvestrant (82%), 5 receiving SERMs (10%), 3 receiving a mTOR inhibitor plus a steroidal AI (6%), and one patient receiving an AI alone. The overall CBR was 44.9% (90% CI: 34.6-57.6, p=0.009), and CBR was similar across following subgroups (PgR+: n=39, 51.3%, 90% CI: 39.6-65.2, p=0.0016; very low sensitivity group: n=17, 58.8%, 90% CI: 42.0-78.8, p=0.003; non-visceral metastases: n=25, 40%, 90% CI; 34.1-65.9, p=0.0175). However, there were not statistically significant CBR in PgR- (n=10, 20.0%, 90% CI; 8.73-50.7, p=0.617), fulvestrant subgroup (n=40, 40.0 %, 90% CI; 29.2-54.2, p=0.063), low sensitive group (n=32, 37.5%, 90% CI; 26.0-53.6, p=0.1326), and visceral metastases (n=24, 48%, 90%CI; 28.2-60.3 p=0.072). The median PFS was 7.1 mo. (95% CI: 5.6-10.6). Conclusion:This study shows that 2nd line ETs was effective and might be a valid option in the sequence of treatments for postmenopausal women with ABC with low sensitivity to initial ET. It was suggested that PgR and visceral metastasis were significant predictive factors for CBR.
Citation Format: Araki K, Fujisawa T, Sakamaki K, Kikawa Y, Iwamoto T, Sangai T, Shien T, Takao S, Nishimura R, Takahashi M, Aihara T, Mukai H, Taira N. Sequential second line endocrine therapy is still an effective strategy for postmenopausal ER+ and HER2- advanced breast cancer with low sensitivity to initial endocrine therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-09.