TY - JOUR
T1 - Adjuvant lapatinib for women with early-stage HER2-positive breast cancer
T2 - A randomised, controlled, phase 3 trial
AU - Goss, Paul E.
AU - Smith, Ian E.
AU - O'Shaughnessy, Joyce
AU - Ejlertsen, Bent
AU - Kaufmann, Manfred
AU - Boyle, Frances
AU - Buzdar, Aman U.
AU - Fumoleau, Pierre
AU - Gradishar, William
AU - Martin, Miguel
AU - Moy, Beverly
AU - Piccart-Gebhart, Martine
AU - Pritchard, Kathleen I.
AU - Lindquist, Deborah
AU - Chavarri-Guerra, Yanin
AU - Aktan, Gursel
AU - Rappold, Erica
AU - Williams, Lisa S.
AU - Finkelstein, Dianne M.
N1 - Funding Information:
PEG has received speaker's honoraria from GlaxoSmithKline and Pfizer and is supported by the Avon Foundation (New York, NY, USA). MP-G's institution has received grants from GlaxoSmithKline and Roche; MP-G has received consultancy fees and honoraria from Roche. BE has received fees from GlaxoSmithKline for participating in advisory boards. KIP and IES have received honoraria and consulting fees from Roche and GlaxoSmithKline. GA and ER are employees of GlaxoSmithKline and own stocks and shares of GlaxoSmithKline. JO'S is a consultant to GlaxoSmithKline. FB is consultant to GlaxoSmithKline and has received fees from GlaxoSmithKline for participating in advisory boards.
PY - 2013/1
Y1 - 2013/1
N2 - Background: Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the 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 33 centres 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 ClinicalTrials.gov, number NCT00374322. 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.
AB - Background: Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the 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 33 centres 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 ClinicalTrials.gov, number NCT00374322. 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.
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U2 - 10.1016/S1470-2045(12)70508-9
DO - 10.1016/S1470-2045(12)70508-9
M3 - Article
C2 - 23234763
AN - SCOPUS:84871712684
SN - 1470-2045
VL - 14
SP - 88
EP - 96
JO - The lancet oncology
JF - The lancet oncology
IS - 1
ER -