Abstract PS13-31: Prospective observational study to explore the effectiveness of eribulin as first- or second- line chemotherapy in patients with HER2-negative hormone-resistant advanced or metastatic breast cancer (KBCRN A001: E-SPEC study)
Authors: Fujimoto Yuri , Kikawa Yuichiro , Kotake Takeshi , Tsuyuki Shigeru , Takahara Sachiko , Yamashiro Hiroyasu , Yoshibayashi Hiroshi , Takada Masahiro , Yasuoka Rie , Yamagami Kazuhiko , Suwa Hirofumi , Okuno Toshitaka , Nakayama Ichiro , Kato Tatsuji , Ogura Nobuko , Moriguchi Yoshio , Ishiguro Hiroshi , Kagimura Tatsuo , Taguchi Tetsuya , Sugie Tomoharu , Toi Masakazu 
Published: February 2021

Abstract
BackgroundEribulin (E) is a chemotherapeutic drug that prolongs overall survival (OS) of patients with HER2-negative advanced or metastatic breast cancer (AMBC), mainly in multi-line chemotherapy (ChT) or later. However, the effectiveness and optimal scheduling of E remain unclear. We prospectively investigated the impact of E use in 1st- and 2nd-line ChT (early E) for patients with endocrine-resistant AMBC.
Methods In this multi-institutional prospective cohort study, we registered patients with hormone receptor-positive AMBC who relapsed during or within 6 months after ending adjuvant endocrine therapy, were refractory to at least one previous endocrine therapy, or patients with triple negative AMBC. The endpoints were 1st-line OS (OS1), 2nd-line OS (OS2), and 3rd-line OS (OS3), defined as the time from the start of treatment to death. In addition, the time from the start of 1st-line ChT to death was also analyzed for 2nd-line and 3rd-line ChT groups. In addition to E therapy, oral FU-based therapies (FU) and anthracycline or taxane-based therapies (A/T) were also analyzed (ClinicalTrial.gov number, NCT02551263).
Results Between June 2015 and July 2017, a total of 201 patients were enrolled, and full analysis was conducted for 180 patients. The median OS1, OS2, and OS3 of all patients was 2.69, 1.74, and 1.13 years, respectively. Major patient characteristics are described in the Table. Concurrent or maintenance endocrine therapy was used by 14.9%, 31.6%, and 12.9% of patients receiving E, FU and A/T in 1st-line ChT, respectively. The median OS of patients using E was OS1: 2.25 years (N=47), OS2: 1.75 years (N=70) and OS3: 0.94 years (N=16). The median OS of patients using A/T was OS1: 2.60 years (N=70), OS2: 1.69 years (N=44) and OS3: 0.96 years (N=49). The median OS of patients using FU was OS1: 3.49 years (N=57), OS2: 2.33 years (N=27), and OS3: 1.45 years (N=24). The time from the start of 1st-line ChT to death was 2.58 and 3.18 years among patients who received E in 2nd- and 3rd-line ChT, respectively. Multivariate analysis of patients who used 1st-line and 2nd-line E demonstrated that higher LDH (≥300) (HR 3.50, 95% CI 1.78-6.73; p&lt;0.001), brain metastasis (HR 2.64, 95% CI 1.02-6.83; p=0.045) and smoker (HR 2.33, 95% CI 1.20-4.53; p=0.013) were associated with shorter OS. Overall, OS data for E were comparable to those for A/T. While OS tended to be better for FU, patient characteristics for 1st-line ChT showed that FU was often used for patients with less aggressive AMBC. We also present data on second progression-free survival and new metastasis-free survival, prognostic factor analysis and prognostic factor-adjusted comparison, and predictive factor analysis for early E.
Conclusions This prospective observational study of AMBC patients showed that E and A/T had similar survival outcomes in each treatment line. While FU led to relatively longer survival, it was often used for patients with less aggressive AMBC. Analysis data on survival outcomes will also be presented.
Patient characteristics according to 1st-line therapyE (n=47)Oral FU based (n=57)A/T based (n=70)Median age (IQR)61(54-71)64(51-68)59(48-66)Triple negative, n (%)15(31.9)11(19.3)23(32.9)Disease-free interval, n (%)&lt;2 years15(31.9)9(15.8)12(17.1)2-5 years12(25.5)18(31.6)15(21.4)5-8 years4(8.5)9(15.8)9(12.9)&gt;8years3(6.4)10(17.5)8(11.4)Stage49(19.1)9(15.8)23(32.9)(neo) Adjuvant chemotherapy, n (%)30(63.8)36(63.2)32(45.7)Metastatic sites at 1st-line ChT, n (%)Liver16(34.0)12(21.1)22(31.4)Lung15(31.9)17(29.8)25(35.7)Bone24(51.1)27(47.3)36(51.4)Brain6(12.8)1(1.8)2(2.9)
Citation Format: Yuri Fujimoto, Yuichiro Kikawa, Takeshi Kotake, Shigeru Tsuyuki, Sachiko Takahara, Hiroyasu Yamashiro, Hiroshi Yoshibayashi, Masahiro Takada, Rie Yasuoka, Kazuhiko Yamagami, Hirofumi Suwa, Toshitaka Okuno, Ichiro Nakayama, Tatsuji Kato, Nobuko Ogura, Yoshio Moriguchi, Hiroshi Ishiguro, Tatsuo Kagimura, Tetsuya Taguchi, Tomoharu Sugie, Masakazu Toi. Prospective observational study to explore the effectiveness of eribulin as first- or second- line chemotherapy in patients with HER2-negative hormone-resistant advanced or metastatic breast cancer (KBCRN A001: E-SPEC study) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-31.