Dual HER2-Targeting Treatments for Postmenopausal Women With Metastatic Breast Cancer
Dual HER2-targeting drugs with hormone therapy seems to be more beneficial than single HER2 blockade with hormone therapy for postmenopausal women with HER2-positive, hormone receptor–positive metastatic breast cancer, according to the findings of the ALTERNATIVE trial, published in the Journal of Clinical Oncology. The study, led by William Gradishar, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, showed the combination of lapatinib, trastuzumab, and an aromatase inhibitor to be an effective chemotherapy-sparing treatment alternative for this patient population.
The phase III multicenter clinical trial analyzed 355 postmenopausal women with metastatic breast cancer determined to be HER2- and hormone receptor–positive. They were randomized to one of three drug regimens: lapatinib, trastuzumab, and an aromatase inhibitor; trastuzumab and an aromatase inhibitor; or lapatinib and an aromatase inhibitor.
Superior progression-free survival was found in patients treated with the two HER2-targeting therapies compared with those who received trastuzumab and an aromatase inhibitor (11 vs. 5.7 months, with a hazard ratio of 0.62 vs. 0.45). As for the two single-targeted regimens, the median progression-free survival was longer with lapatinib than with trastuzumab (8.3 vs 5.7 months, with a hazard ratio of 0.71). In addition, the overall response rate, clinical benefit rate, and overall survival all the dual HER2-blocking regimen.
In terms of toxicity, diarrhea, rash, nausea, and paronychia were common adverse events (at least 15%) with the combination of lapatinib and trastuzumab. Although 69% of patients experienced diarrhea with dual HER2 blockade, most of the cases were grade 1 or 2.