The use of neoadjuvant systemic therapy for the treatment of breast cancer provides the patient with disease-free survival and overall-survival rates similar to adjuvant systemic therapy and improves breast conservation because of tumor response to therapy. The preoperative setting is unique in that it allows the clinician to monitor response to therapy in previously untreated patients. In patients with HER2-positive breast tumors, pathological complete response (pCR) at the time of surgery appears to be associated with improved disease outcome in several clinical trials.12 Results from the NeOAdjuvant Herceptin (NOAH) trial demonstrated that the addition of trastuzumab to neoadjuvant chemotherapy almost doubled the pathologic complete response, improved overall response rates, and reduced the risk of relapse, disease progression, or death in women with locally advanced or inflammatory breast cancer.13 Similar results were found in the the Taxol Epirubicin Cyclophosphamide Herceptin NeOadjuvant (TECHNO) trial.14
Most recently, the NeoAdjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) study evaluated the efficacy of lapatinib, trastuzumab, and their combination as neoadjuvant therapy in women with HER2-positive early breast cancer.12 In this randomized, parallel-group, open-label, Phase 3 trial, women from 23 countries with HER2-positive primary breast cancer with tumors greater than 2cm in diameter were randomly assigned to either lapatinib 1500mg PO daily (N=154), or trastuzumab with a loading dose of 4mg/m2 IV and subsequent doses of 2mg/kg IV every week (N=149), or lapatinib 1000mg PO daily plus trastuzumab (loading dose of 4mg/m2 IV and subsequent doses of 2mg/kg IV every week) (N=152). Each drug treatment regimen was given for the first 6 weeks, and then paclitaxel 80mg/m2 IV weekly was added to each regimen for an additional 12 weeks prior to definitive surgery. Patients underwent breast surgery within 4 weeks after the last dose of paclitaxel. After surgery, the patients received adjuvant therapy followed by the same targeted therapy in the neoadjuvant phase to 52 weeks. The primary end point, which was pCR rate with the absence of tumor cells at the time of surgery, was significantly higher in patients receiving combination lapatinib/trastuzumab therapy (51.3%) compared to patients receiving trastuzumab alone (29.5%) or lapatinib alone (24.7%). There was no significant difference in the pCR between the lapatinib group (24.7%) and the trastuzumab group (29.5%). Clinical response rates at the end of the first 6 weeks for combination therapy and lapatinib therapy were superior to trastuzumab alone. This may have been a result of the time for trastuzumab to reach steady-state. All three treatment regimens appeared to be well tolerated, with diarrhea (23.4%) and liver-enzyme alterations (17.5%) reported more frequently with lapatinib.