Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) study confirms use of trastuzumab for HER2-positive breast cancer
Analysis of results from the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) study reinforces findings that support trastuzumab (Herceptin) as the standard-of-care treatment for HER2-positive breast cancer. ALTTO, the world's largest study of the two treatments for this cancer, involved more than 8,000 women. The findings were presented at the European Society for Medical Oncology (ESMO) 2014 Congress, in Madrid, Spain.
The study revealed that when used as a single HER2-targeted therapy in addition to standard chemotherapy, trastuzumab offers a better outcome than does lapatinib (Tykerb). Edith A. Perez, MD, deputy director at large at the Mayo Clinic Cancer Center and director of the Breast Cancer Translational Genomics Program at Mayo Clinic in Jacksonville, Florida, presented the study results.
Perez is co-chair of the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) study. The phase III clinical trial, which tested combinations of the two drugs or use of the drugs by themselves, in addition to standard chemotherapy, enrolled 8,381 participants at 946 medical centers in 44 countries.
A key finding from ALTTO showed that lapatinib, when used in addition to trastuzumab as part of dual therapy, did not offer any statistically significant benefit to patients, such as disease-free survival or overall survival. Dual blockade using two anti-HER2 drugs only increased toxicity, explained Perez.
This new analysis compared use of lapatinib or trastuzumab alone, as well as outcome in disease-free patients who were offered trastuzumab as adjuvant treatment after being treated with lapatinib alone.
The researchers found that trastuzumab offered a better outcome compared with lapatinib alone. After 4.5 years of follow-up, 14% of patients taking trastuzumab experienced at least one disease event, compared with 18% of patients who were taking lapatinib. A disease event is defined as breast cancer recurrence anywhere in the body, a new cancer, or death of any cause.
However, cardiac safety was good in both groups, and there was no difference in the rate of development of brain metastasis, said Perez.
The researchers also showed that switching from lapatinib to trastuzumab offered a benefit to patients. Of the 2,100 patients in the lapatinib arm, 52% received at least one dose of trastuzumab.
"ALTTO was and is a very important global trial. All patients were carefully managed, and we demonstrated better overall outcomes than anticipated," she said. "We demonstrated that lapatinib's activity appeared to be lower than that of trastuzumab in the adjuvant setting, that there was a trend for additional benefit if those patients were switched to trastuzumab, that cardiac safety was better than predicted, and that the number of brain metastases appeared similar for the patients who received either lapatinib or trastuzumab."
Perez added that patients are still being followed, and the research team is investigating tumor and blood specimens to discover and analyze potential biomarkers for treatment efficacy.