Introduction and aims: Lapatinib (L) is a TKI of EGFR and HER2. The inhibition of these two pathways can affect tumor growth by reducing the EGFR-dependent proliferative stimulus, by restoring apoptosis, and possibly by enhancing sensitivity to chemotherapy (CT). On these premises, the combination of L with CT or CT and trastuzumab (T) is promising. We have therefore designed a phase II randomized trial to evaluate activity and safety of this combination as preoperative therapy for HER2+ operable breast cancer (BC). Primary endpoint: %of pCR. Secondary aims: breast objective response, breast conservative surgery, safety, molecular responses, gene expression related to pCR. Patients and methods: After a core biopsy for diagnosis, biomarker evaluation and storage of fresh tissue for molecular analyses, patients with HER2+ stage II-IIIA BC are randomized to: Arm A: CT+T; Arm B: CT+L; Arm C: CT+T+L. CT consists in: paclitaxel 80 mg/sqm wkly for 12 wks, followed by 4 courses of FEC (5FU 600 mg/smq + Epirubicin 75 mg/sqm + Cyclophosphamide 600 mg/sqm iv) q3wks. T is administered at the dose of 2 mg/kg wkly in arms A and C; L is administered at 1500 mg po daily in arm B, and at 1000 mg po daily in arm C. Both T and L are administered throughout the duration of CT. The following biomarkers are evaluated at baseline, and at surgery: EGFR, HER2, pTEN, pAKT, pMAPK, Apoptosis (TUNEL Test), Ki67. Sample size: assuming a 50% increase in the pCR rate for the CT+T+L arm vs CT+T or CT+L, in the first stage 52 patients will be enrolled; in case we observe 16 pCR, additional 68 patients will be enrolled, for a total of 120 patients (Simon’s design). Results 12 patients have been randomized so far. Preliminary safety data will be presented at the meeting.
Preliminary safety data of preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2-positive operable breast cancer / Guarneri, Valentina; Frassoldati, A; Piacentini, Federico; Cagossi, K; Cavanna, L; Michelotti, A; Jovic, Gordana; Giovannelli, Simona; Ficarra, G; Oliva, C; Conte, Pierfranco. - In: BREAST CANCER RESEARCH. - ISSN 1465-5411. - STAMPA. - 9:(2007), pp. P23-P23. (Intervento presentato al convegno VII Madrid Breast Cancer Conference tenutosi a Madrid nel JUN 20-22, 2007) [10.1186/bcr1729].