The lapatinib-alone vs. trastuzumab-alone arm was closed in early 2011 due to futility, and results from that arm will be presented later this year.
The current efficacy results were based on 6,281 women, with 4,613 receiving the anti-HER2 drugs after completing chemotherapy.
Lapatinib was associated with significant increases in diarrhea, hepatobiliary events, and skin rash or erythema. This may explain why only 60-78% of patients in the lapatinib-containing arms received at least 85% of protocol-specified dose, Dr. Piccart-Gebhart said during the formal presentation of the late-breaking abstract.
Importantly, cardiac toxicity was "remarkably low in all treatment arms" at less than 1%, she said. This was true despite 97% of women receiving anthracyclines.
A primary cardiac event, defined as cardiac death or severe congestive heart failure (New York Heart Association class III-IV), occurred in 0.97% of patients on lapatinib plus trastuzumab, 0.25% on trastuzumab followed by lapatinib, and 0.86% on trastuzumab alone. Any cardiac event was reported in 3.7%, 2.4%, and 4.5%, respectively.
Follow-up in ALTTO will continue, with a protocol-specified updated efficacy analysis planned in 2 years.
ALTTO was sponsored by the National Cancer Institute and GlaxoSmithKline, maker of lapatinib. Dr. Piccart-Gebhart reported employment or a leadership role with PharmaMar, and a consulting/advisory role and honoraria from several companies, but not GSK. Dr. Sledge reported serving as a board member for Syndax and as a consultant for Roche-Genentech, Symphogen, and Seattle Genetics. Dr. Perez reported having no financial disclosures.