TY - JOUR
T1 - Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial
AU - Perez, Edith A.
AU - Suman, Vera J.
AU - Davidson, Nancy E.
AU - Sledge, George W.
AU - Kaufman, Peter A.
AU - Hudis, Clifford A.
AU - Martino, Silvana
AU - Gralow, Julie R.
AU - Dakhil, Shaker R.
AU - Ingle, James N.
AU - Winer, Eric P.
AU - Gelmon, Karen A.
AU - Gersh, Bernard J.
AU - Jaffe, Allan S.
AU - Rodeheffer, Richard J.
PY - 2008/3/10
Y1 - 2008/3/10
N2 - Purpose: To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial. Patients and Methods: Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab then trastuzumab alone (arm C). Left ventricular ejection fraction (LVEF) was evaluated at registration and 3, 6, 9, and 18 to 21 months. Results: Of 2,992 patients completing AC, 5.0% had LVEF decreases disallowing trastuzumab (decrease below normal: 2.4%, decrease > 15%: 2.6%). There were 1,944 patients with satisfactory or no LVEF evaluation who proceeded to post-AC therapy. Cardiac events (congestive heart failure [CHF] or cardiac death [CD]): arm A, n = 3 (2 CHF, 1 CD); arm B, n = 19 (18 CHF, 1 CD); arm C, n = 19 (all CHF); 3-year cumulative incidence: 0.3%, 2.8%, and 3.3%, respectively. Cardiac function improved in most CHF cases following trastuzumab discontinuation and cardiac medication. Factors associated with increased risk of a cardiac event in arms B and C: older age (P < .003), prior/current antihypertensive agents (P = .005), and lower registration LVEF (P < .033). Incidence of asymptomatic LVEF decreases requiring holding trastuzumab was 8% to 10%; LVEF recovered and trastuzumab was restarted in approximately 50%. Conclusion: The cumulative incidence of post-AC cardiac events at 3 years was higher in the trastuzumab-containing arms versus the control arm, but by less than 4%. Older age, lower registration LVEF, and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC.
AB - Purpose: To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial. Patients and Methods: Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab then trastuzumab alone (arm C). Left ventricular ejection fraction (LVEF) was evaluated at registration and 3, 6, 9, and 18 to 21 months. Results: Of 2,992 patients completing AC, 5.0% had LVEF decreases disallowing trastuzumab (decrease below normal: 2.4%, decrease > 15%: 2.6%). There were 1,944 patients with satisfactory or no LVEF evaluation who proceeded to post-AC therapy. Cardiac events (congestive heart failure [CHF] or cardiac death [CD]): arm A, n = 3 (2 CHF, 1 CD); arm B, n = 19 (18 CHF, 1 CD); arm C, n = 19 (all CHF); 3-year cumulative incidence: 0.3%, 2.8%, and 3.3%, respectively. Cardiac function improved in most CHF cases following trastuzumab discontinuation and cardiac medication. Factors associated with increased risk of a cardiac event in arms B and C: older age (P < .003), prior/current antihypertensive agents (P = .005), and lower registration LVEF (P < .033). Incidence of asymptomatic LVEF decreases requiring holding trastuzumab was 8% to 10%; LVEF recovered and trastuzumab was restarted in approximately 50%. Conclusion: The cumulative incidence of post-AC cardiac events at 3 years was higher in the trastuzumab-containing arms versus the control arm, but by less than 4%. Older age, lower registration LVEF, and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC.
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U2 - 10.1200/JCO.2007.13.5467
DO - 10.1200/JCO.2007.13.5467
M3 - Article
C2 - 18250349
AN - SCOPUS:41649083764
SN - 0732-183X
VL - 26
SP - 1231
EP - 1238
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -