A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

摘要

Background: The use of HER2 targeting therapy has revolutionized the treatment of HER2 positive breast cancers. Here, we?investigate whether a sequential approach to dual HER2 blockade of lapatinib followed by trastuzumab will result in improved?clinical outcomes.Methods: This was a single institution, open label, single arm, phase II trial in women with HER2 positive breast cancer.?Volunteers were treated with sequential neoadjuvant doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) for 4?cycles followed by docetaxel (100 mg/m2) concurrent with lapatinib (1,250 mg) (TL) daily for 21 days for four cycles before?definitive surgery. The primary end point was pathologic complete response (pCR).Results: The study accrued only 21 of the 71 planned patients from 2/28/2007 to 5/25/2010. All patients (100%) experienced?down staging. The pCR rate was 41% (7/18). 11 patients had tumor size of T3 or greater, 3 of which experienced pCR and only 1?underwent breast conservation (lumpectomy). The most common hematologic AE (all grades) was anemia 17/21 (81%). There?were no incidences of grade 3 or 4 anemia. 10 of 21 (48%) patients experience a non-hematologic grade 3 AE. The most common?non-hematologic AEs (all grades) were irregular menses 20/21 (95%) and hand-foot-skin reactions 20/21 (95%). No increase?cardiac abnormalities were noted. The DFS at data cut off was 87.5%.Conclusion: The provocative pCR and DFS results in this high risk locally advanced patient population should be viewed with?caution given results of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation study (ALTTO) clinical trial.