The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) study, which is evaluating various anti-HER2 therapy approaches in breast cancer, has discontinued the single-agent lapatinib (Tykerb) arm, according to study sponsor GlaxoSmithKline.
Following a preplanned interim analysis based on 256 events, the study’s data safety and monitoring committee (DSMB) indicated that “the lapatinib-alone arm is unlikely to meet the prespecified criteria to demonstrate noninferiority to trastuzumab (Herceptin)-alone with respect to disease-free survival,” according to a recenty issued company statement.
Other Study Arms
The three other arms of the ALTTO trial, which involves more than 8,000 patients in 50 countries, will continue uninterrupted. This includes trastuzumab monotherapy (52 weeks), trastuzumab (12–18 weeks) followed by lapatinib (28–34 weeks) and trastuzumab in combination with lapatinib (52 weeks). Patients also receive chemotherapy (anthracyclines, taxane, or docetaxel/carboplatin) during the first 12 or 18 weeks of treatment.
“Preliminary data showed that lapatinib appeared to be inferior to single-agent trastuzumab for disease-free survival, as it crossed the boundary for noninferiority. The patients on lapatinib alone appeared not to be doing as well as the control treatment,” said Edith A. Perez, MD, coprincipal investigator of ALTTO, in a presentation at the 2011 Breast Cancer Symposium in San Francisco that coincided with the announcement.1 “Based on the information provided by the DSMB, the leadership of ALTTO concluded that the rest of the study remains as written,” she added.
“Patients receiving single-agent lapatinib should discuss their options to receive adjuvant trastuzumab, which will be provided free of charge to patients if there are problems with insurance coverage,” she said.
Dr. Perez noted that these findings differ from what was observed in the NeoALTTO trial, which found no statistically significant difference for single-agent lapatinib and trastuzumab (plus chemotherapy) and neoadjuvant treatment. “Importantly, this calls into question whether we can use comparisons in the neoadjuvant setting to predict what we will see in the adjuvant setting,” she said. ■
Disclosure: Dr. Perez receives research funding from Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Novartis, and Sanofi-Oncology.
1. Perez E: HER2-directed therapy. 2011 Breast Cancer Symposium. Welcome and General Session VII: Advances in Molecular Classification of Breast Cancer and Clinical Implications. Presented September 10, 2011.