Adding Adjuvant Lapatinib to Trastuzumab Not Effective for HER2+ Breast Cancer

Adjuvant treatment that included lapatinib did not significantly improve disease-free survival compared with trastuzumab alone and added toxicity in patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, a new study published online ahead of print in the Journal of Clinical Oncology has shown.¹

Although previous research demonstrated that lapatinib plus trastuzumab improved outcomes for patients with HER2-positive metastatic breast cancer and increased the pathological complete response in patients, their efficacy in the adjuvant setting remained unclear.

“The main hypothesis of ALTTO was that hitting HER2 with 2 targeted therapies should be better than using only one; because toxicity of simultaneous dual HER2 blockade could be an issue, one strategy that was also tested was the sequential administration of trastuzumab and lapatinib,” wrote principal investigator Martine Piccart-Gebhart, MD, PhD, professor of oncology at the Université Libre de Bruxelles in Belgium.

Therefore, researchers designed the phase 3 Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial to compare lapatinib plus trastuzumab with trastuzumab alone in patients with early HER2-positive disease.

For the study, researchers enrolled 8381 patients and randomly assigned them to receive 1 year of adjuvant therapy with trastuzumab; lapatinib; trastuzumab then lapatinib; or lapatinib plus trastuzumab.

Patients in the trastuzumab group received a loading dose of 4 mg/kg once and then 2 mg/kg weekly in addition to chemotherapy or a loading dose of 8 mg/kg once and then 6 mg/kg every 3 weeks when administered alone. 

Patients in the lapatinib arm received 750 mg/day of lapatinib during chemotherapy or 1500 mg/day when given alone. Participants in the sequential arm received 12 weekly doses of intravenous trastuzumab followed by a 6-week washout period, and then 34 weeks of lapatinib 1500 mg/day.

Those in the combination arm received trastuzumab plus lapatinib 750 mg/day during chemotherapy, which was dose-escalated to 1000 mg/day after chemotherapy had been completed.