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Eur J Cancer. 2016 Jan;53:144-54. doi: 10.1016/j.ejca.2015.10.012. Epub 2015 Dec 24.

A European Organisation for Research and Treatment of Cancer randomized, double-blind, placebo-controlled, multicentre phase II trial of anastrozole in combination with gefitinib or placebo in hormone receptor-positive advanced breast cancer (NCT00066378).

Author information

1
EORTC-Headquarters, Medical Department, Brussels, Belgium. Electronic address: konstantinos.tryfonidis@eortc.be.
2
Acıbadem Üniversitesi İç Hastalıkları/Tıbbi Onkoloji, Turkey. Electronic address: gabasaran@gmail.com.
3
EORTC-Headquarters, Statistical Department, Belgium. Electronic address: jan.bogaerts@eortc.be.
4
Institute Bergonie, Bordeaux, France. Electronic address: M.Debled@bordeaux.unicancer.fr.
5
GZA Sint Augustinus, Antwerp, Belgium. Electronic address: Luc.dirix@telenet.be.
6
Ctr Becquerel-Rouen, France. Electronic address: jean-christophe.thery@chb.unicancer.fr.
7
Radboudumc Nijmegen/Maastricht UMC+, Netherlands. Electronic address: vcg.tjan.heijnen@mumc.nl.
8
ZNA Middelheim, Belgium. Electronic address: Danielle.VandenWeyngaert@zna.be.
9
University Clinic Golnik, Slovenia. Electronic address: Tanja.Cufer@klinika-golnik.si.
10
Institute Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
11
NHS-Lothian, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: D.Cameron@ed.ac.uk.

Abstract

BACKGROUND:

Preclinical data suggest that epidermal growth factor receptor (EGFR) inhibitors (e.g. gefitinib) can delay endocrine resistance in breast cancer. A double-blind, placebo-controlled, phase II trial investigated whether adding gefitinib (G) to anastrozole (A) would improve outcome in advanced breast cancer (ABC).

METHODS:

Postmenopausal pre-treated hormone receptor-positive ABC patients (locally recurrent or metastatic) were 1:1 randomized to A (1 mg/d) plus G 250 mg/d or plus placebo (P). Patients who had prior treatment with an aromatase inhibitor in metastatic setting or with trastuzumab, anti-EGFR or anti-VEGF agents were excluded. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal. Progression-free survival (PFS) rate at 1 year was assessed according to Response Evaluation Criteria in Solid Tumours, version 1.0.

RESULTS:

Of 108 planned patients, 71 were recruited (36 in A/G and 35 in A/P). The trial closed prematurely due to slow recruitment; 31 patients had prior chemotherapy and 53 prior endocrine therapy (all except one received tamoxifen); 60% in adjuvant and 16% in metastatic setting received tamoxifen; 59 patients had visceral disease. Median follow-up was 18 months. PFS rate at 1 year was 35% for A/G and 32% for A/P arm. Objective responses were six (22%) in the A/G and nine (28%) in the A/P arm. Median duration of response was 13.8 and 18.6 months in the A/G and A/P arms, respectively. Fatigue (35%), diarrhoea (31%), rash (32%), dry skin (27%), and arthralgia/myalgia (27%) were the commonest adverse events in the A/G arm.

CONCLUSIONS:

This phase II study, although prematurely closed, did not show a signal that adding G to A improves PFS at 1 year and its use is not supported. Gastrointestinal and skin toxicities were more pronounced with G resulting in premature therapy interruption in almost 1 in 3 patients (ClinicalTrials.gov number, NCT00066378).

KEYWORDS:

Anastrozole; Endocrine resistance; Gefitinib; Metastatic breast cancer

PMID:
26724641
DOI:
10.1016/j.ejca.2015.10.012
[Indexed for MEDLINE]

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