Trastuzumab

The phase III NeOAdjuvant Herceptin (NOAH) study randomly assigned patients with HER2-positive locally advanced or inflammatory breast cancers to undergo preoperative chemotherapy with or without 1 year of trastuzumab therapy.[114][Level of evidence A1]

The phase III NeOAdjuvant Herceptin (NOAH) study randomly assigned patients with HER2-positive locally advanced or inflammatory breast cancers to undergo preoperative chemotherapy with or without 1 year of trastuzumab therapy.[114][Level of evidence A1]

Study results confirmed that the addition of trastuzumab to preoperative chemotherapy resulted not only in improved clinical responses (87% vs. 74%) and pathological responses (breast and axilla, 38% vs. 19%) but also in EFS, the primary outcome.[114][Level of evidence A1]

The phase III NeOAdjuvant Herceptin (NOAH) study randomly assigned patients with HER2-positive locally advanced or inflammatory breast cancers to undergo preoperative chemotherapy with or without 1 year of trastuzumab therapy.[114][Level of evidence A1]

After a median follow-up of 5.4 years, the EFS benefit was 58% with the addition of trastuzumab to chemotherapy (95% CI, 48%–66%) and 43% (95% CI, 34%–52%) in patients in the chemotherapy group. The unadjusted HR for EFS between the two randomized HER2-positive treatment groups was 0.64 (95% CI, 0.44–0.93; two-sided log-rank P = .016). EFS was strongly associated with pCR in patients who received trastuzumab.[115]

The phase III NeOAdjuvant Herceptin (NOAH) study randomly assigned patients with HER2-positive locally advanced or inflammatory breast cancers to undergo preoperative chemotherapy with or without 1 year of trastuzumab therapy.[114][Level of evidence A1]

Symptomatic cardiac failure occurred in two patients who received concurrent doxorubicin and trastuzumab for two cycles. Close cardiac monitoring of left ventricular ejection fraction (LVEF) and the total dose of doxorubicin not exceeding 180 mg/m2 accounted for the relatively low number of declines in LVEF and only two cardiac events. For more information, see the Cardiac Toxic Effects With Adjuvant Trastuzumab section.[114][Level of evidence B1]

Due to concern about coadministration of trastuzumab and anthracyclines, a phase III trial (Z1041 [NCT00513292]) randomly assigned patients with operable HER2-positive breast cancer to receive trastuzumab sequential to or concurrent with the anthracycline component (5-FU, epirubicin, and cyclophosphamide [FEC]) of the preoperative chemotherapy regimen.[116][Level of evidence B3]

Due to concern about coadministration of trastuzumab and anthracyclines, a phase III trial (Z1041 [NCT00513292]) randomly assigned patients with operable HER2-positive breast cancer to receive trastuzumab sequential to or concurrent with the anthracycline component (5-FU, epirubicin, and cyclophosphamide [FEC]) of the preoperative chemotherapy regimen.[116][Level of evidence B3]

The primary outcome was pCR. There was no significant difference in pCR rate in the breast between the arms (56.5% sequential, 54.2% concurrent; difference, 2.3%; 95% CI, -9.3 to 13.9).

Due to concern about coadministration of trastuzumab and anthracyclines, a phase III trial (Z1041 [NCT00513292]) randomly assigned patients with operable HER2-positive breast cancer to receive trastuzumab sequential to or concurrent with the anthracycline component (5-FU, epirubicin, and cyclophosphamide [FEC]) of the preoperative chemotherapy regimen.[116][Level of evidence B3]

Asymptomatic declines in LVEF during preoperative chemotherapy were identified in similar proportions of patients in each arm.

Due to concern about coadministration of trastuzumab and anthracyclines, a phase III trial (Z1041 [NCT00513292]) randomly assigned patients with operable HER2-positive breast cancer to receive trastuzumab sequential to or concurrent with the anthracycline component (5-FU, epirubicin, and cyclophosphamide [FEC]) of the preoperative chemotherapy regimen.[116][Level of evidence B3]

DFS and OS were secondary outcomes. After median follow-up of 5.1 years, there was no difference in DFS (HR, 1.02; 95% CI, 0.56−1.83; P = .96) or OS (HR, 1.17; 95% CI, 0.48−2.88; P = .73) between the sequential and concurrent arms.[117]

Due to concern about coadministration of trastuzumab and anthracyclines, a phase III trial (Z1041 [NCT00513292]) randomly assigned patients with operable HER2-positive breast cancer to receive trastuzumab sequential to or concurrent with the anthracycline component (5-FU, epirubicin, and cyclophosphamide [FEC]) of the preoperative chemotherapy regimen.[116][Level of evidence B3]

Based on these findings, concurrent administration of trastuzumab with anthracyclines is not warranted.