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

Abstract:

BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSIONS:The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION:Clinical Trial Registration: UMIN-CTR as UMIN000007074.

journal_name

Br J Cancer

authors

Mukai H,Yamaguchi T,Takahashi M,Hozumi Y,Fujisawa T,Ohsumi S,Akabane H,Nishimura R,Takashima T,Park Y,Sagara Y,Toyama T,Imoto S,Mizuno T,Yamashita S,Fujii S,Uemura Y

doi

10.1038/s41416-020-0815-9

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

1747-1753

issue

12

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-0815-9

journal_volume

122

pub_type

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