RC0639: phase II study of paclitaxel, trastuzumab, and lapatinib as adjuvant therapy for early stage HER2-positive breast cancer

Springer Science and Business Media LLC - Tập 138 - Trang 427-435 - 2013
Alvaro Moreno-Aspitia1, Amylou C. Dueck2, Ismael Ghanem-Cañete3, Tejal Patel4, Shaker Dakhil5, David Johnson5, Sandra Franco6, Stephen Kahanic7, Gerardo Colon-Otero1, Kathleen S. Tenner8, Richard Rodeheffer8, Ann E. McCullough2, Robert B. Jenkins8, Frances M. Palmieri9, Donald Northfelt, Edith A. Perez1
1Division of Hematology and Oncology, Mayo Clinic, Jacksonville, USA
2Mayo Clinic, Scottsdale, USA.
3Hospital Universitario 12 de Octubre, Madrid, Spain
4Methodist Cancer Center, Houston, USA
5Cancer Center of Kansas, Wichita, USA
6Clinica del Country, Bogota, Columbia
7Siouxland Hematology/Oncology, Sioux City, USA
8Mayo Clinic, Rochester, USA
9Sarah Cannon Research Institute, Nashville, USA

Tóm tắt

Lapatinib adds to the efficacy of trastuzumab in preclinical models and also in the neo-adjuvant setting. This study assesses the safety and feasibility of adding lapatinib to paclitaxel and trastuzumab (THL) as part of the adjuvant therapy for HER2-positive breast cancer (HER2+ BC). In this single-arm phase II study, patients with stages I–III HER2+ BC received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. The primary endpoint was symptomatic congestive heart failure, secondary endpoints included overall safety. A total of 109 eligible patients were enrolled. Median follow-up is 4.3 years. No patients experienced congestive heart failure while on treatment. Mean left ventricular ejection fraction at baseline and at the end of THL were 63.6 % (N = 109, SD = 5.7) and 59.8 % (N = 98, SD = 8.1), respectively [mean change −3.95 % (N = 98, SD = 8.3), p < 0.001]. One hundred and two patients initiated post-AC treatment; of them, 31 % experienced grade 3 (no G4) diarrhea with lapatinib at 750 mg/day. The addition of lapatinib to paclitaxel and trastuzumab following AC does not add cardiac toxicity. Lapatinib dose of 750 mg/day in combination with standard chemotherapy plus trastuzumab has acceptable overall tolerability.

Tài liệu tham khảo

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