Cardiac Toxic Effects With Adjuvant Trastuzumab

In the HERA (BIG-01-01) trial, severe congestive heart failure (CHF) (New York Heart Association class III–IV) occurred in 0.6% of patients treated with trastuzumab.[10] Symptomatic CHF occurred in 1.7% of patients in the trastuzumab arm and 0.06% of patients in the observation arm.

In the NSABP B-31 trial (NCT00004067), 31 of 850 patients in the trastuzumab arm had confirmed symptomatic cardiac events, compared with 5 of 814 patients in the control arm.[11] The 3-year cumulative incidence of cardiac events for trastuzumab-treated patients was 4.1%, compared with 0.8% of patients in the control arm (95% CI, 1.7%–4.9%).

In the NCCTG-N9831 trial, 39 cardiac events were reported in the three arms over a 3-year period. The 3-year cumulative incidence of cardiac events was 0.35% in arm A (no trastuzumab), 3.5% in arm B (trastuzumab after paclitaxel), and 2.5% in arm C, (trastuzumab concomitant with paclitaxel).

In the AVENTIS-TAX-GMA-302 (BCIRG 006) trial (NCT00021255), clinically symptomatic cardiac events were detected in 0.38% of patients in the doxorubicin and cyclophosphamide (AC)/docetaxel (AC-D) arm, 1.87% of patients in the AC/docetaxel/trastuzumab (AC-DH) arm, and 0.37% of patients in the docetaxel/carboplatin/trastuzumab (DCbH) arm.[12] There was also a statistically significant higher incidence of asymptomatic and persistent decrease in left ventricular ejection fraction (LVEF) in the AC-DH arm than with either the AC-D or DCbH arms.

In the FINHER trial, none of the patients who received trastuzumab experienced clinically significant cardiac events. LVEF was preserved in all of the women receiving trastuzumab, but the number of patients receiving adjuvant trastuzumab was very low.[13]