Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): A randomised, open-label, multicentre, phase 3 trial
The Lancet - Early Online Publication, 01/17/2012
Clinical Article
Baselga J et al. –Dual inhibition of HER2 might be a valid approach to treatment of HER2–positive breast cancer in the neoadjuvant setting.
Methods- In this parallel groups, randomised, open–label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2–positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/m2, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab
- Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors
- Anti–HER2 therapy alone was given for first 6 weeks; weekly paclitaxel (80 mg/m2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken
- After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks
- Primary endpoint was rate of pathological complete response (pCR), analysed by intention to treat
- 154 patients received lapatinib, 149 trastuzumab, and 152 the combination
- pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3%; 95% CI 43·1—59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5%; 22·4—37·5]; difference 21·1%, 9·1—34·2, p=0·0001)
- No significant difference in pCR between the lapatinib (38 of 154 patients [24·7%, 18·1—32·3]) and the trastuzumab groups
- No major cardiac dysfunctions occurred
- Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4%]) and lapatinib plus trastuzumab (32 [21·1%]) than with trastuzumab (three [2·0%])
- Grade 3 liver–enzyme alterations were more frequent with lapatinib (27 [17·5%]) and lapatinib plus trastuzumab (15 [9·9%]) than with trastuzumab (11 [7·4%])
