Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer: results of a randomised Phase 2 study

• Published in: British journal of cancer Vol. 122; no. 12; pp. 1747 - 1753
• Main Authors: Mukai, Hirofumi, Yamaguchi, Takeshi, Takahashi, Masato, Hozumi, Yasuo, Fujisawa, Tomomi, Ohsumi, Shozo, Akabane, Hiromitsu, Nishimura, Reiki, Takashima, Tsutomu, Park, Youngjin, Sagara, Yasuaki, Toyama, Tatsuya, Imoto, Shigeru, Mizuno, Toshiro, Yamashita, Satoshi, Fujii, Satoshi, Uemura, Yukari
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.06.2020; Nature Publishing Group UK
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Chemotherapy, Adjuvant - methods; Clinical trials; Cyclophosphamide; Cyclophosphamide - administration & dosage; Epirubicin; Epirubicin - administration & dosage; ErbB-2 protein; Female; Humans; Ki-67 Antigen - analysis; Ki-67 Antigen - biosynthesis; Middle Aged; Monoclonal antibodies; Neoadjuvant Therapy - methods; Paclitaxel; Paclitaxel - administration & dosage; Patients; Receptor, ErbB-2 - biosynthesis; Targeted cancer therapy; Trastuzumab; Trastuzumab - administration & dosage; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-0815-9

The effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumour expression after initial therapy, relative to that of standard chemotherapy, has not been evaluated. Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumour 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 were 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. Ki-67 early responder is defined as the absolute Ki-67 value that was <10%, and the percentage of Ki-67-positive tumour cells was reduced by >30% compared with before treatment. Early Ki-67 responders continued to receive the same treatment, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate. A total of 237 patients were randomised. 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 was inferior to that in the control arm (44.1%; 31.4-56.7; P = 0.025). The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer. Clinical Trial Registration: UMIN-CTR as UMIN000007074.