Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial

详细信息    查看全文

• 作者：Prof Paul E Goss ; MD^a ; ^{pgoss@partners.org} ; Prof Ian E Smith ; MD^b ; Joyce O'Shaughnessy ; MD^c ; Prof Bent Ejlertsen ; MD^d ; Prof Manfred Kaufmann ; MD^e ; Frances Boyle ; MBBS^f ; Prof Aman U Buzdar ; MD^g ; Prof Pierre Fumoleau ; MD^h ; Prof William Gradishar ; MDⁱ ; Prof Miguel Martin ; MD^j ; Beverly Moy ; MD^a ; Martine Piccart-Gebhart ; MD^k ; Prof Kathleen I Pritchard ; MD^l ; Deborah Lindquist ; MD^m ; Yanin Chavarri-Guerra ; MD^a ; Gursel Aktan ; MDⁿ ; Erica Rappold ; BSNⁿ ; Lisa S Williams ; MSc^o ; Prof Dianne M Finkelstein ; PhD^a ; on behalf of the TEACH investigators ^&dagger ;
• 刊名：Lancet Oncology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：14
• 期：1
• 页码：88-96
• 全文大小：316 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Background

Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab¡ªthe standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis.

Methods

This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 405 centres in 33 countries with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with , number .

Findings

Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47¡¤4 months (range 0¡¤4-60¡¤0) in the lapatinib group and 48¡¤3 (0¡¤7-61¡¤3) in the placebo group, 210 (13 % ) disease-free survival events had occurred in the lapatinib group versus 264 (17 % ) in the placebo group (hazard ratio [HR] 0¡¤83, 95 % CI 0¡¤70-1¡¤00; p=0¡¤053). Central review of HER2 status showed that only 2490 (79 % ) of the randomised women were HER2-positive. 157 (13 % ) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17 % ) of 1260 in the placebo group had a disease-free survival event (HR 0¡¤82, 95 % 0¡¤67-1¡¤00; p=0¡¤04). Serious adverse events occurred in 99 (6 % ) of 1573 patients taking lapatinib and 77 (5 % ) of 1574 patients taking placebo, with higher incidences of grade 3-4 diarrhoea (97 [6 % ] vs nine [<1 % ]), rash (72 [5 % ] vs three [<1 % ]), and hepatobiliary disorders (36 [2 % ] vs one [<1 % ]).

Interpretation

Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population. However, exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival. Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or cannot receive adjuvant trastuzumab.

Funding

GlaxoSmithKline.