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).

Authors

null

C. T. Dang

Memorial Sloan-Kettering Cancer Center, New York, NY

C. T. Dang , P. G. Morris , S. Patil , C. Chen , A. Abbruzzi , R. Lehman , R. Steingart , L. Norton , C. Hudis

Organizations

Memorial Sloan-Kettering Cancer Center, New York, NY

Research Funding

Pharmaceutical/Biotech Company

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) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and addition of L (1000mg orally daily) x 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.

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Abstract Details

Meeting

2011 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer - HER2/ER

Track

Breast Cancer

Sub Track

HER2+

Clinical Trial Registration Number

NCT00591851, NCT00482391

Citation

J Clin Oncol 29: 2011 (suppl; abstr 579)

Abstract #

579

Poster Bd #

6E

Abstract Disclosures