Long-term cardiac safety and outcomes of dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).

Abstract

579 Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). Dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) improves survival compared to the every 3 week schedule and can be combined w/ anti-HER2 Rx w/ no increased risk of cardiotoxicity. We report the long-term incidence of NYHA Class III/IV CHF in 2 phase II studies. Methods: We conducted a retrospective review of pts w/ HER2 + BC treated at MSKCC on two trials: In trial A - pts received dd AC (60/600 mg/m2) × 4 → T (175mg/m2) × 4 (w/ pegfilgrastim) w/ H × 1 year. Trial B differed w/ use of weekly T (80mg/m2) × 12 and addition of L (1000mg orally daily) × 1 year. Left ventricular ejection fraction (LVEF) was assessed by a multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts w/ a median age of 49 yrs (range, 27-72) and median baseline LVEF of 68% (range 55-81%); 41/68 (69%) had node + BC; 2 had neoadjuvant Rx. Trial B enrolled 66 pts w/ a median age of 48 yrs (range 28-73) and median baseline LVEF of 68% (range 52-81%); 45/53 (83%) had node + BC; 13 had neoadjuvant Rx. Of these, 11 (16%) and 10 (15%) pts had pre-existing hypertension; 23 (33%) and 27 (41%) pts were smokers; 23 (33%) and 28 (42%) pts received left-sided radiation, in Trials A and B, respectively. Now at a median follow-up of 62 months and 36 months, only one (1.4%) and 2 (3%) pts developed CHF in Trial A and Trial B, respectively. No additional CHF events have occurred since the initial reports (median follow-up 2 yrs each). Overall, the crude disease-free survival rates are 93% (65/70) and 94% (62/66), and the crude overall survival rates are 97% (68/70) and 97% (64/66) in Trials A and B, respectively. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is not associated w/ an additional risk of CHF. This is consistent w/ the long-term cardiac toxicity reported by randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). Survival outcomes are encouraging.