Breast Cancer Health Center

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In September 2011, the ALTTO trial was amended to discontinue the lapatinib alone arm of the trial. The Independent Data Monitoring Committee of the trial determined that the patients assigned to the lapatinib alone arm were not likely to do as well as the patients assigned to the trastuzumab alone control arm. Final results of this trial are pending.

Cardiotoxicity with adjuvant trastuzumab

In the HERA (BIG-01-01) trial, severe congestive heart failure (CHF NYHA class III-IV) occurred in 0.6% of patients treated with trastuzumab.[196] Symptomatic CHF occurred in 1.7% and 0.06% of patients in the trastuzumab and observation arms, respectively. Fifty-one patients experienced a confirmed left ventricular ejection fraction (LVEF) decrease (defined as an EF decrease of >10 points from baseline to an LVEF <50%) with trastuzumab, which recovered or stabilized within 3 to 6 weeks of initial treatment in 86% of cases. In the NSABP B-31 (NCT00004067) trial, 31 of 850 patients in the trastuzumab arm had confirmed symptomatic cardiac events, compared with 5 of 814 patients in the control arm.[205] 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%). Asymptomatic decline in LVEF (defined by >10% decline or to 55%) occurred in 17% of patients in the trastuzumab arm (95% CI, 15%-20%) and 34% of patients in the control arm (95%CI, 31%-38%), with a HR = 2.1 (95%CI, 1.7-2.6; P < .001). 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 in arm A was 0.35% (no trastuzumab), arm B, 3.5% (trastuzumab following paclitaxel) and arm C, 2.5% (trastuzumab concomitant with paclitaxel).

In the AVENTIS-TAX-GMA-302 (BCIRG 006) trial, clinically symptomatic cardiac events were detected in 0.38% of patients in the AC-D arm, 1.87% of patients in the AC-DH arm, and 0.37% of patients in the DCbH arm.[200] There was also a statistically significant higher incidence of asymptomatic and persistent decrease in LVEF in the AC-DH arm than with either the AC-D or DCbH arms. No cardiac deaths were reported in the AVENTIS-TAX-GMA-302 trial.

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

Treatment options for HER2-positive early breast cancer:

• Standard treatment is 1 year of adjuvant trastuzumab therapy. Results of the 1 year versus 2 years of trastuzumab of the HERA trial are awaited, as are the results of the Protocol of Herceptin Adjuvant with Reduced Exposure (INCA-PHARE) trial, which compared 1 year versus 6 months of adjuvant trastuzumab.