Evandro de Azambuja1, Noam Ponde2,3, Marion Procter4, Priya Rastogi5, Reena S Cecchini6, Matteo Lambertini2,7, Karla Ballman6, Alvaro Moreno Aspitia8, Dimitrios Zardavas9, Lise Roca10, Richard D Gelber11, Martine Piccart-Gebhart2,9, Thomas Suter12. 1. Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Boulevard de Waterloo, 121 (7th Floor), 1000, Brussels, Belgium. evandro.azambuja@bordet.be. 2. Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Boulevard de Waterloo, 121 (7th Floor), 1000, Brussels, Belgium. 3. AC Camargo Cancer Center, Sao Paulo, Brazil. 4. Frontier Science (Scotland), Kincraig, UK. 5. NRG Oncology, and The University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 6. NRG Oncology, and the University of Pittsburgh, Pittsburgh, PA, USA. 7. IRCCS Ospedale Policlinico San Martino and University of Genova, GENOVA, Italy. 8. Mayo Clinic, Jacksonville, FL, USA. 9. Breast International Group (BIG), Brussels, Belgium. 10. Institut Regional du Cancer Montpellier Val d'Aurelle, Montpellier, France. 11. Dana-Farber Cancer Institute, Harvard Medical School, Harvard TH Chan School of Public Health, and Frontier Science and Technology Research Foundation, Boston, MA, USA. 12. University Hospital Bern, Bern, Switzerland.
Abstract
BACKGROUND: Trastuzumab-associated cardiotoxicity remains an issue for patients with HER2-positive breast cancer. This pooled analysis of 3 adjuvant trials investigated the incidence, timing, impact on treatment completion, and risk factors for trastuzumab-associated cardiotoxicity. METHODS: This is an individual patient data level pooled analysis of HERA, NSBAP B-31, and NCCTG 9831 (Alliance Trials). Definitions of cardiac events were as per each individual study. RESULTS: A total of 7445 patients enrolled in the 3 trials were included in the analysis, of which 4017 were in the trastuzumab and 3428 in the control (observation) arms, respectively. Median follow-up exceeded 10 years (119.2-137.2 months). Nearly all patients (97.4%) in the trastuzumab arms received anthracycline-based chemotherapy. In total, 452 patients in the trastuzumab arms experienced a cardiac event (11.3%), with most being mildly symptomatic or asymptomatic left ventricular ejection fraction (LVEF) decrease (351 patients, 8.7%). Severe congestive heart failure was more common in the trastuzumab arm (2.3%) than in the control arm (0.8%). Most cardiac events occurred during trastuzumab treatment (78.1%) and cardiac events were the main cause of discontinuation across the sample (10.0%); nevertheless, a large majority of patients completed trastuzumab treatment (76.2%). Baseline risk factors that were significantly associated with the development of cardiac events were baseline LVEF < 60%, hypertension, body mass index > 25, age ≥ 60 and, non-Caucasian ethnicity. CONCLUSION: One year of trastuzumab increases the risk of cardiac events, though most consist of asymptomatic or mildly symptomatic LVEF drops. Adjuvant trastuzumab should be considered a safe treatment from a cardiac standpoint for most patients. Trastuzumab-associated cardiotoxicity is the main cause of discontinuation and further research is needed to individualize prevention and management.
BACKGROUND: Trastuzumab-associated cardiotoxicity remains an issue for patients with HER2-positive breast cancer. This pooled analysis of 3 adjuvant trials investigated the incidence, timing, impact on treatment completion, and risk factors for trastuzumab-associated cardiotoxicity. METHODS: This is an individual patient data level pooled analysis of HERA, NSBAP B-31, and NCCTG 9831 (Alliance Trials). Definitions of cardiac events were as per each individual study. RESULTS: A total of 7445 patients enrolled in the 3 trials were included in the analysis, of which 4017 were in the trastuzumab and 3428 in the control (observation) arms, respectively. Median follow-up exceeded 10 years (119.2-137.2 months). Nearly all patients (97.4%) in the trastuzumab arms received anthracycline-based chemotherapy. In total, 452 patients in the trastuzumab arms experienced a cardiac event (11.3%), with most being mildly symptomatic or asymptomatic left ventricular ejection fraction (LVEF) decrease (351 patients, 8.7%). Severe congestive heart failure was more common in the trastuzumab arm (2.3%) than in the control arm (0.8%). Most cardiac events occurred during trastuzumab treatment (78.1%) and cardiac events were the main cause of discontinuation across the sample (10.0%); nevertheless, a large majority of patients completed trastuzumab treatment (76.2%). Baseline risk factors that were significantly associated with the development of cardiac events were baseline LVEF < 60%, hypertension, body mass index > 25, age ≥ 60 and, non-Caucasian ethnicity. CONCLUSION: One year of trastuzumab increases the risk of cardiac events, though most consist of asymptomatic or mildly symptomatic LVEF drops. Adjuvant trastuzumab should be considered a safe treatment from a cardiac standpoint for most patients. Trastuzumab-associated cardiotoxicity is the main cause of discontinuation and further research is needed to individualize prevention and management.
Entities:
Keywords:
Breast cancer; Cardiotoxicity; LVEF; Trastuzumab
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