A dual anti-HER2 blockade with lapatinib and trastuzumab resulted in modest, nonsignificant disease-free survival improvements over adjuvant trastuzumab alone for patients with early human epidermal growth factor 2 (HER2)-positive breast cancer, according to results of the phase III ALTTO trial.
Disease-free survival (DFS) improved slightly with lapatinib and trastuzumab over trastuzumab alone (555 DFS events; hazard ratio, 0.84; 97.5% CI, 0.70-1.02; P = .048). The 4-year overall survival was 95% for lapatinib and trastuzumab and 94% for trastuzumab alone (HR, 0.80; 95% CI, 0.62-1.03; P = .078) (J Clin Oncol. 2015 Nov 23. [doi: 10.1200/JCO.2015.62.1797]).
The marginal benefit observed in lapatinib arms was offset by additional toxicity. The incidence of diarrhea, mostly grade 1 or 2, was higher in the lapatinib arms and was responsible for treatment discontinuation at a rate from 4% to 9% depending on the lapatinib arm. Slightly more than half of the patients in lapatinib arms experienced rash, compared with about 20% in the trastuzumab arm. Primary or secondary cardiac events were rare in any treatment arm.
Previous studies showed benefit from the dual blockade for heavily pretreated patients with advanced disease, particularly in the hormone receptor–negative population.
“We did not expect to observe the degree of toxicity (especially diarrhea), which ultimately reduced the level of enthusiasm for lapatinib in the adjuvant setting,” wrote Dr. Martine J. Piccart-Gebhart, professor of oncology at Université Libre de Bruxelles and director of the medicine department at the Jules Bordet Institute in Brussels, and her colleagues.
The phase III ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial evaluated 8,381 patients with completely excised invasive nonmetastatic HER2-positive breast cancer from 945 sites in 44 countries.
The 4-year overall survival rates of approximately 95% illustrate the steady improvement in clinical outcomes of early breast cancer. The addition of adjuvant lapatinib to trastuzumab produced a modest treatment effect with additional toxicity, and is not clinically meaningful, according to investigators. The standard of care remains trastuzumab for one year.
Research was supported by GlaxoSmithKline and by the National Cancer Institute of the National Institutes of Health. Dr. Piccart-Gebhart reported consulting or advisory roles with Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Symphogen, Synthon, and Verastem. Several of her coauthors reported ties to industry.