Final results of a phase II randomized trial of neoadjuvant anthracycline-taxane chemotherapy plus lapatinib, trastuzumab, or both in HER2-positive breast cancer (CHER-LOB trial).

Background: This is a randomized phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab and lapatinib in HER2 positive, stage II-IIIA breast cancer patients. Primary aim of the study is the percentage pathological complete response (pCR), defined as complete disappearance of invasive tumor in breast and axillary nodes. Methods: chemotherapy (CT) consists of weekly paclitaxel x 12 followed by FE75C x 4. Pts randomized to arm A receive CT plus weekly trastuzumab; in arm B pts receive CT plus lapatinib 1250 mg po daily; in arm C pts receive CT plus weekly trastuzumab and lapatinib 750 mg po daily. The study sample size has been calculated according to the two-step Simon’s design. The overall planned accrual was 120 pts. P95HER2 expression will be measured by bioTheranostics, Inc (San Diego) to explore if there is a clinically relevant difference in the pCR rate according to p-95 status. Gene expression profile analysis to identify a predictive signature is ongoing. Results: 121 pts have been randomized as of November 2010. Pts characteristics are the following: median age 49 yrs (26-68 yrs); stage IIA 32%, IIB 50%; IIIA 18%; ER and or PgR positivity: 59%. Eighty pts have completed surgery and are evaluable for response: 50 pts (62.5%) received breast conservation (BCS). A conversion from mastectomy to BCS was observed in 23/44 pts initially candidate to mastectomy (conversion rate: 52%). The pCR rate is 36.2% (28% in arm A, 32% in arm B, and 48% in arm C). By using a 30% cutoff for p95 positivity, in a preliminary analysis on 48 cases, 57% resulted as p-95 positive. In this preliminary analysis, the pCR rate in 15 trastuzumab treated pts is 86% in p-95-negative and 13% in p-95-positive cases. Mean Left ventricular ejection fraction (range) at baseline was 62% (52%-77%), 61% (44%-78%) after 12-13 weeks, and 61% (44%-74%) at the end of therapy. No patient had symptomatic cardiac events. Conclusions: Preliminary activity data are promising, and cardiac safety data are reassuring. Final results per treatment arm, along with definitive biomarker correlations will be presented at the meeting.