Abstract P4-21-03: A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer

Abstract

Abstract As for the HER2-positive breast cancer, there are many cases to be effective for neoadjuvant chemotherapy in comparison with other intrinsic subtypes. However, pCR is not provided by neoadjuvant chemotherapy in all cases. [Aim] This study evaluated the effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, relative to that of standard chemotherapy in patients with HER2-positive breast cancer. [patients and methods] Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumor biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab was continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Early Ki-67 responders continued to received paclitaxel plus trastuzumab for a total of 12 doses, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide every 3 weeks for three cycles with once-weekly trastuzumab for a total of 12 doses. The primary endpoint was the pathological complete response (pCR) rate. [Results] When 237 patients were enrolled, an interim analysis was conducted in 200 patients. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm (23.6%; 95% CI, 12.4 to 34.9) was inferior to that in the control arm (44.1%; 31.4 to 56.7; p=0.025). A strong correlation was not found between the Ki-67 reduction rate and the clinical response rate (Spearman's correlation coefficient 0.22). pCR rate among Ki-67 early non-responders and responders TotalpCR nn%95%CIKi-67 early non responderControl arm59264431.4-56.7 Ki-67 response guided arm55132312.4-34.9Ki-67 early responderControl arm21104726.3-69.0 Ki-67 response guided arm2084018.5-61.5 Conclusions: The pCR rate in the Ki-67 arm was inferior to that in the control arm. A therapeutic strategy that switches chemotherapy, based on Ki-67 tumor expression after initial therapy, was not effective. The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer. Citation Format: Takahashi M, Nishiyama Y, Hara F, Naito Y, Baba M, Sasaki M, Sato M, Watanabe K, Uemura Y, Yamaguchi T, Mukai H. A randomized phase II study of Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-03.