(ChemotherapyAdvisor) – For patients with HER2-positive operable breast cancer, dual-HER2 inhibition using preoperative chemotherapy plus trastuzumab and lapatinib was superior to chemotherapy plus either agent alone, the Phase 2 CHER-LOB study investigators reported in the Journal of Clinical Oncology online April 9.
In this noncomparative trial, 121 patients with HER2–positive, stage 2 to 3A operable breast cancer were randomly assigned to one of three arms: arm A received a 4mg loading dose of trastuzumab followed by 2mg weekly (n=36); arm B received lapatinib 1,500mg orally daily (n=39); and arm C received trastuzumab and lapatinib 1,000mg orally daily (n=46). All arms received weekly paclitaxel (80mg/m2) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every three weeks. The primary goal was to estimate percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes).
Rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B, and C, respectively. The pCR rates were 25% in arm A, 26.3% in arm B, and 46.7% in arm C (exploratory P=0.019). Patients receiving lapatinib had more frequently occurring dermatologic and hepatic toxicities and diarrhea; the protocol was amended to reduce the lapatinib dose to 1,250mg/day in arm B and to 750mg/day in arm C. No episodes of congestive heart failure were observed.
“Chemotherapy plus trastuzumab and lapatinib induced a pCR rate of 46.7%, which represents a relative increase of 80% in the pCR rate achieved with the same chemotherapy plus either trastuzumab or lapatinib,” they wrote. Although the pCR end point is an early surrogate for outcome, not survival — “the data from this trial add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of patients with HER2-positive breast cancer.”