Because the researchers determined it futile to demonstrate noninferiority of lapatinib compared with trastuzumab, the adjuvant lapatinib arm was closed. A post-hoc time-dependent analysis showed that patients in the trastuzumab arm had a 33% reduced risk for having signs and symptoms of cancer compared with those in the lapatinib arm (HR, 0.67; 95% CI, 0.49 – 0.91).

Results showed that at a median follow-up of 4.5 years, patients in the combination arm had a 16% reduced risk of cancer presence compared with the trastuzumab alone arm (555 disease-free events; HR, 0.84; 97.5% CI, 0.70 – 1.02; P = .048); however, this figure was not statistically significant because it did not reach the .025 significance level.

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Researchers did not identify any particular subgroup that seemed to benefit from lapatinib plus trastuzumab. There was also no significant difference in 4-year overall survival among the combination, sequential, or trastuzumab-alone groups.

“Dual HER2 blockade has an effect but of modest magnitude (the benefit was not statistically significant) and there is still hope that using 2 antibodies, namely trastuzumab with pertuzumab, might be successful (this last combination is being tested in the APHINITY trial, which will be reported in 2017),” Dr. Piccart-Gebhart noted.

In regard to safety, adverse events occurred more frequently in the lapatinib-containing arms than in the trastuzumab arm. Patients in the lapatinib-containing arms experienced more diarrhea, dermatologic toxicities, and hepatobiliary events.

The findings suggest that adjuvant trastuzumab for 1 year should remain the standard of care for patients with early HER2-positive breast cancer.

“In retrospect, too much faith was placed in lapatinib as a single agent, which was viewed in 2007 as an interesting alternative to trastuzumab because the drug does not require frequent visits to the hospital, as it is oral and because its mechanism of action is very different from the one of trastuzumab,” Dr. Piccart-Gebhart wrote.

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Lapatinib is already approved by the U.S. Food and Drug Administration in combination with capecitabine, for the treatment of patients with HER2-positive advanced or metastatic breast cancer who have received prior therapy, including an anthracycline, a taxane, and trastuzumab.2 It is also indicated in combination with letrozole for the treatment of postmenopausal women with hormone receptor-positive, HER2-positive metastatic breast cancer for whom hormonal therapy is indicated.


  1. Piccart-Gebhart M, Holmes E, Baselga J, et al. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: Results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial [published online ahead of print November 23, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.62.1797.
  2. Tykerb [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2014.