7 yr followup adjuvant herceptin clinical trial shows late developmt of heart failure

[Lani]

is rare. Risk/benefit analysis still strongly favors adjuvant herceptin

J Clin Oncol. 2012 Sep 17. [Epub ahead of print]
Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.
Romond EH, Jeong JH, Rastogi P, Swain SM, Geyer CE Jr, Ewer MS, Rathi V, Fehrenbacher L, Brufsky A, Azar CA, Flynn PJ, Zapas JL, Polikoff J, Gross HM, Biggs DD, Atkins JN, Tan-Chiu E, Zheng P, Yothers G, Mamounas EP, Wolmark N.
Source
Edward H. Romond, Jong-Hyeon Jeong, Priya Rastogi, Sandra M. Swain, Charles E. Geyer Jr, Louis Fehrenbacher, Adam Brufsky, Catherine A. Azar, Patrick J. Flynn, John L. Zapas, Jonathan Polikoff, Howard M. Gross, David D. Biggs, James N. Atkins, Ping Zheng, Greg Yothers, Eleftherios P. Mamounas, and Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Center; Jong-Hyeon Jeong, Ping Zheng, and Greg Yothers, Graduate School of Public Health, University of Pittsburgh; Priya Rastogi and Adam Brufsky, University of Pittsburgh School of Medicine (UPMC), Magee-Women's Hospital; Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA; Edward H. Romond, Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY; Sandra M. Swain, Washington Cancer Institute, Washington Hospital Center, Washington, DC; Charles E. Geyer Jr, University of Texas Southwestern Medical Center, Dallas; Michael S. Ewer, The University of Texas MD Anderson Cancer Center, Houston, TX; Vikas Rathi, Bon Secours Health System, Midlothian, VA; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Jonathan Polikoff, Kaiser Permanente, San Diego, San Diego, CA; Catherine A. Azar, Community Clinical Oncology Program (CCOP), Colorado Cancer Research Program, Denver, CO; Patrick J. Flynn, CCOP, Metro-Minnesota, St Louis Park, MN; John L. Zapas, Franklin Square Hospital Center, Baltimore, MD; Howard M. Gross, CCOP, Dayton; Eleftherios P. Mamounas, Aultman Hospital Cancer Center, Canton, OH; David D. Biggs, CCOP, Christiana Care Health Services, Newark, DE; James N. Atkins, CCOP Southeast Cancer Control Consortium, Goldsboro, NC; and Elizabeth Tan-Chiu, Florida Cancer Research Institute, Plantation, FL.
Abstract
PURPOSECardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. PATIENTS AND METHODSIn National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified.ResultsAt 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. CONCLUSIONThe late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
PMID: 22987084 [PubMed - as supplied by publisher]