Liposome-encapsulated doxorubicin plus cyclophosphamide followed by trastuzumab plus docetaxel as neoadjuvant therapy for HER2-positive breast cancer (BC): A multicenter single-arm phase II study.

Abstract

641 Background: Trastuzumab combined to sequential chemotherapy with taxanes and anthracyclines as primary treatment achieved high rates of pathologic complete response (pCR) in HER2 positive BC. Liposome-encapsulated doxorubicin (DLNP) shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab associated with chemotherapy for early or locally advanced HER2 positive BC. Methods: Primary objective of the study was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Preoperative treatment included DLNP (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Patients (pts) were scheduled to receive adjuvant trastuzumab (8 mg/mq loading dose, then 6 mg/mq iv) every 3 weeks for 12 cycles and radiation and hormonal therapy according to guidelines. Results: From December 2005 to September 2011, 43 pts were treated at 3 centers in Italy. 39 out of 43 pts were evaluable for the purpose of the study. Median age was 53 years (range: 31-78). The majority of pts had cT2 (63%), grade 3 (93%), N+ (77%) ER positive (56%) and MIB-1 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. The histological regression score (Von Minckwitz G, J Clin Oncol 2012) is shown in the Table. A significant correlation between MIB-1 ≥20% at baseline and pCR was observed (p=0.018). Pts with pCR had a time to response (29.4 weeks, 95% CI 28-31) lower than pts without pCR (32.9 weeks, 95% CI 27-39). No cardiac toxicity or discontinuation of trastuzumab was reported. After a median follow-up of 30 months only 2 pts relapsed, both with pCR. Conclusions: This study confirms the high activity of trastuzumab combined with chemotherapy based on anthracyclines and taxanes as primary treatment for HER2 positive BC. DLNP is an active and safe option to minimize cardiotoxicity. [Table: see text]