Open label, randomized, phase II study of pertuzumab (P) in patients (pts) with metastatic breast cancer (MBC) with low expression of HER2

Abstract

3068 Background: P is the 1st of a new class of targeted therapeutics known as HER-dimerization inhibitors (HDI). It blocks ligand-associated heterodimerization of HER2 with other HER kinase family members, thereby inhibiting intracellular signaling. Preclinical activity of P in breast cancer has been shown to be independent of the HER2 expression level. In this study the primary endpoint was response rate according to RECIST. Secondary endpoints were: rate of stable disease (SD), toxicity profile, pharmacokinetics (PK). Methods: 79 pts in total were randomized to receive P every 3 weeks as an IV infusion either at 420 mg with a loading dose of 840 mg (arm A) or at 1050 mg (arm B). Selection criteria were: progressing MBC with low HER2 expression, anthracycline pretreatment, ≤ 2 chemotherapy regimens for MBC and LVEF ≥ 50%. Results: Out of 79 recruited pts, 78 were included in the intent to treat population. In arm A 2 partial responses (PR) and 18 SD were observed in 41 pts. In arm B 14 SD were observed in 37 pts. Overall, 6 out of 78 pts responded or had SD for > 6 months. Most frequent adverse events were: diarrhea grade (G) 1 & 2 51%, G3 8%, fatigue G 1 & 2 35%, G3 2%, nausea G 1 & 2 31%, G3 1% and vomiting G 1 & 2 23%, G3 4%. Drops in LVEF of ≥10% and to below 50% were observed in 3 pts (1 case of congestive heart failure) in arm A & 3 pts in arm B. PK data supports a fixed dose of P administered every 3 weeks. Conclusions: No obvious relationship between dose and activity or toxicity was observed. The monoclonal antibody P administered IV every 3 weeks is safe and well tolerated but there is evidence of limited activity in this BC study. A combination (either chemo or hormonal) or patient selection strategy may be investigated in the future. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Nordic, Roche Genentech, Roche Aventis, Lilly Oncology, Pierre Fabre, Roche Roche