Safety and Activity Report of a Randomized Phase II Trial of Preoperative Anthracycline-Based Chemotherapy Plus Lapatinib, Trastuzumab or Both in HER2 Positive Breast Cancer: CHERLOB Trial.

Introduction: We have designed a randomized phase II trial of preoperative sequential taxanes-anthracyclines in combination with trastuzumab, lapatinib, or both trastuzumab and lapatinib in HER2 positive, stage II-IIIA breast cancer patients. Primary aim of the study is the percentage of pathological complete response (pCR) as defined as complete disappearance of invasive tumor in both breast and axillary nodes.Methods: chemotherapy (CT) consists of paclitaxel 80 mg/m2 weekly x 12 weeks followed by FE75C x 4 cycles administered every 3 weeks. Patients randomized to arm A receive CT plus weekly trastuzumab; in arm B patients receive CT plus lapatinib 1500 mg po daily; in arm C patients receive CT plus weekly trastuzumab and lapatinib 1000 mg po daily. Trastuzumab and lapatinib are administered throughout the entire CT plan. The study sample size has been calculated according to the two steps Simon's design. The overall planned accrual is 120 patients. Following the second safety report from the Independent Data Monitoring Committee on the first 30 evaluable patients, due to the occurrence of grade 3 diarrhea in 20% and in 41% of the patients randomized to arm B and C respectively, lapatinib doses have been reduced to 1250 mg in arm B and 750 mg in arm C.Results: 66 patients have been randomized: 20 in arm A, 20 in arm B, and 26 in arm C. Median age is 50 years (range 27-66). The overall non hematologic toxicity of grade (G) >1, as reported as maximum toxicity per patient, is as follows: diarrhea G2 29%, G3 22%; skin rash G2 29%, G3 7%; hepatobiliary events G2 10%, G3 5%, G4 3%.Left ventricular ejection fraction (LVEF) has been evaluated at baseline, after 12-13 weeks, and at the end of therapy. Mean LVEF% (range) was 62% (52%-77%), 61% (44%-78%) and 61% (53%-74%) respectively. No patient had symptomatic cardiac events. Forty-five patients underwent surgery, and are evaluable for response: 67% of the patients received breast conserving surgery. A pCR in breast and axillary nodes has been observed in 39% of the cases.Conclusions: The study accrual is ongoing. The safety of patients randomized following the amendment reducing lapatinib dosage will be presented at the Meeting.