Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer: results of a randomised Phase 2 study
Menée à partir d'échantillons biopsiques prélevés sur 237 patientes atteintes d'un cancer du sein HER2+ et incluses dans un essai de phase II évaluant une chimiothérapie pré-opératoire, cette étude analyse la corrélation entre le pourcentage de réduction, au milieu du traitement, de la proportion de cellules cancéreuses exprimant Ki-67 et le taux de réponse complète afin d'évaluer l'intérêt d'une stratégie thérapeutique basée sur l'indice Ki-67
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.
British Journal of Cancer , résumé, 2020