Two anti-HER2 drugs may be better than one in the neoadjuvant setting

The combination of trastuzumab and lapatinib, two drugs that inhibit HER2, may be better than treatment with either agent alone in the neoadjuvant (preoperative) setting, according to results of a study published in Lancet. “This is the first demonstration that adding a second anti-HER2 therapy, lapatinib, to trastuzumab is superior to trastuzumab alone in patients with early breast cancer,” says Dr. JosĂ© Baselga, who led the study.

The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib were studied in combination and individually in parallel groups, randomised, open-label, phase 3 study. The NeoAdjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) study enrolled 455 patients in 23 countries. Eligibility criteria included primary, early-stage HER2-positive breast cancer without prior treatment. The participants were randomized to one of three treatment arms: anti-HER2 treatment with either intravenous trastuzumab (n=149), oral lapatinib (n=154) or both (n=152) for 6 weeks. Weekly paclitaxel was then added to the regimen for an additional 12 weeks before surgery. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. Pathological complete response (PCR) was the primary endpoint.

In an intention-to-treat analysis, pCR rate was 21% higher in the group given lapatinib and trastuzumab (51.3% had pCR; 95% CI=43.1-59.5) than in the group given trastuzumab alone (29.5% had pCR; 95% CI=22.4-37.5). There was no significant difference in pCR between the lapatinib and the trastuzumab groups. “Dual inhibition of HER2 might be a valid approach to the treatment of HER2-positive breast cancer in the neoadjuvant setting,” conclude the authors. The effect, if any, of this combination on patients’ overall survival, will be reported in a future study.


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