Breast Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage I, II, IIIA, and Operable IIIC Breast Cancer
Table 6. Standard Adjuvant Chemotherapy Regimens for Stage I, II, IIIA, and Operable IIICHER2/neuNon-Overexpressing Breast Cancer continued...
In HER2-overexpressed disease, pilot studies have demonstrated remarkable clinical and pathologic responses when trastuzumab is given preoperatively in combination with chemotherapy. A randomized study in patients with HER2-positive locally advanced or inflammatory breast cancers confirmed that the addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy with sequential doxorubicin plus paclitaxel followed by CMF resulted not only in improved clinical responses (87% vs. 74%) and pathologic responses (38% vs. 19%) but also in the primary outcome: event-free survival (EFS). This was defined as the time from random assignment to disease recurrence or progression—whether local, regional, distant, or contralateral—or death from any cause.
At 3 years, of all of the patients, 71% (95% CI, 61–78) showed improvement in EFS with trastuzumab versus 56% without trastuzumab (95% CI, 46–65), HR, 0.59 (95% CI, 0.38–0.90, P = .013), thereby favoring the addition of trastuzumab. The 3-year OS was 87% versus 79% at the time of the report (P = .114, not significant). Symptomatic cardiac failure developed in two patients receiving 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. (See the Cardiac toxic effects with adjuvant trastuzumab section in this summary.)[Level of evidence: 1iiD]
The role of lapatinib in the neoadjuvant setting was examined in the GeparQuinto [NCT00567554] trial. This phase III trial randomly assigned women with HER2-positive early stage breast cancer to receive chemotherapy with trastuzumab versus chemotherapy with lapatinib with pathologic complete response (pCR) as the primary endpoint.[Level of Evidence: 1iiDiv] pCR in the chemotherapy and lapatinib arm was significantly lower than it was with chemotherapy and trastuzumab (22.7% vs. 30.3%; P = .04). Other endpoints of DFS, relapse-free survival (RFS), and OS have not been reported. The results do not support the use of single-agent lapatinib with chemotherapy in the neoadjuvant setting.
Neoadjuvant therapy with dual HER2 inhibition was studied in the NeoALTTO [NCT00553358] trial.[Level of evidence: 1iiDiv] This phase III trial randomly assigned 455 women with HER2-positive early stage breast cancer (tumor size >2 cm) to receive neoadjuvant lapatinib compared with neoadjuvant trastuzumab compared with neoadjuvant lapatinib plus trastuzumab. This anti-HER2 therapy was given alone for 6 weeks and then weekly paclitaxel was added to the regimen for an additional 12 weeks for all enrolled patients. The primary endpoint of this study was pCR. pCR was significantly higher in the lapatinib plus trastuzumab combination arm (51.3%; 95% CI, 43.1–59.5) than in the trastuzumab alone arm (29.5%; 95% CI, 22.4–37.5). No significant difference in pCR was seen between the lapatinib (24.7%, 95% CI, 18.1–32.3) and trastuzumab groups (difference -4.8%, -17.6–8.2; P = -.34).