Preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2 positive operable breast cancer: results of the randomized phase II CHER-LOB study

Purposes: This is a non-comparative randomized phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in HER2 positive, stage II-IIIA operable breast cancer patients. Primary aim was to estimate the percentage of pathological complete response (pCR; no invasive tumor in breast and axillary nodes).Methods: in the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/sqm) x 12 followed by FE75C x 4 courses q 3 weeks. The patients randomized to arm A received trastuzumab 4 mg loading dose followed by 2 mg weekly; in arm B patients received lapatinib 1500 mg p.o. daily; in arm C, patients received trastuzumab and lapatinib 1000 mg p.o. daily.Results: 121 patients have been randomized. Diarrhea, dermatologic, and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast conserving surgery were 66.7%, 57.9% and 68.9% in arm A, B and C, respectively. The pCR rates were 25% (90%CI 13.1 to 36.9) in arm A, 26.3% (90%CI 14.5 to 38.1) in arm B, 46.7% (90%CI 34.4 to 58.9) in arm C (exploratory p= 0.0187).Conclusions: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared to chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2 positive breast cancer.