Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 518
© 2008 American Society of Clinical Oncology

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Abstract

Preliminary safety results of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2 overexpressed/amplified breast cancer (BCA)

Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA

518

Background: We showed that dd q 2 weekly (w) AC P + Tx1 year (y) as adjuvant treatment (Rx) for patients (pts) with HER2 (+) BCA is safe with a congestive heart failure (CHF) rate of 1/70 pts (in press, JCO 2008). Lapatinib (L) is effective in HER2/neu (+) pts w/ Stage IV BCA and is being tested in randomized adjuvant trials. We are conducting a pilot study of dd AC w P + T + L to determine the cardiac safety and feasibility of this combination. The 1° endpoint is cardiac safety defined as discontinuation of T + L due to 1) cardiac death or 2) CHF. The 2° endpoints are to evaluate toxicities, time to recurrence, overall survival, and to explore the use of serial troponin I and C-reactive protein as predictors of cardiac toxicity. Methods: Pts must have HER2 IHC 3+ or FISH-amplified BCA, LVEF > 50% and no active cardiac disease. Rx consists of AC at 60/600 mg/m²x4 q 2 w (w/ pegfilgrastim 6 mg on day 2) P at 80 mg/m²x12 q w + Tx1 y (H 4 mg/kg load and 2 mg/kg q w during P and 6 mg/kg q 3 w after all chemotherapy is completed); L (1,000 mg daily is begun w/ P +T and continued for 1 y). MUGA is obtained at baseline and at months (mo) 2, 6, 9, and 18. Pts with significant asymptomatic LVEF decline after dd AC based on mo 2 MUGA do not receive T + L; pts with significant asymptomatic LVEF decline during T + L may have T + L held permanently. Results: From March 2007 to January 2008, we enrolled 63 of 100 planned pts. Median (med) age is 45 years (range, 28–73). Med baseline LVEF is 68 % (range, 52–79 %). As of January 5, 2008, 44 pts have had mo 2 MUGA after dd AC w/ a med LVEF of 70% (52–81%) and there have been no significant LVEF declines. 10/63 pts are off study (5 G 3 diarrhea, 1 G 2 diarrhea, 1 G 2 rash, 1 POD, 1 death after AC # 2 from adenovirus, 1 G 2 fatigue after AC # 4). Conclusions: This is the first report demonstrating cardiac safety and feasibility of dd AC w P + T + L. These are the first safety results for the combination arm in the ALLTO trial. Updated results will be available.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genentech, GlaxoSmithKline Bristol-Myers Squibb, Genentech, GlaxoSmithKline Genentech, GlaxoSmithKline

Abstract presentation from the 2008 ASCO Annual Meeting