Phase II study of liposome-encapsulated doxorubicin plus cyclophosphamide, followed by sequential trastuzumab plus docetaxel as primary systemic therapy for breast cancer patients with HER2 overexpression or amplification.
OBJECTIVE
Trastuzumab combined with sequential chemotherapy with taxanes and anthracyclines as primary systemic therapy achieved high rates of pathologic complete response (pCR). Non-pegylated liposome-encapsulated doxorubicin (NPLD) has shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab with sequential chemotherapy for early or locally advanced HER2 positive BC.


METHODS
Preoperative treatment included NPLD (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. Primary endpoint was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Clinical staging was exploratory evaluated by CT-PET.


RESULTS
43 pts were treated from december 2005 to September 2011, 39 of them were evaluable for the purpose of study. Median age was 53 years (range: 31-78), the majority of pts had tumour stage cT2 (63%), tumour grade 3 (86%), clinical nodes involvement N+ (77%), ER positive (56%) and Ki-67 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. There was an association between Ki-67 ≥20% at baseline and pCR (p = 0.018). No cardiac toxicity or discontinuation of trastuzumab was reported. CT-PET modified the clinical stage for 10 patients showing new loco-regional lymph nodes.


CONCLUSIONS
This study confirms that integrating anti-HER2 therapy in primary treatment for HER2 positive breast cancer is active. NPLD is a safe option to minimize cardiotoxicity.
Department of Oncology, Hospital "S. Maria degli Angeli", Pordenone, Italy.
S
S
Saracchini
L
L
Foltran
F
F
Tuccia
A
A
Bassini
S
S
Sulfaro
E
E
Micheli
A
A
Del Conte
M
M
Bertola
M
M
Gion
M
M
Lorenzon
S
S
Tumolo
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D043823:Taxoids / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D000077143:Docetaxel; D004317:Doxorubicin; D019788:Fluorodeoxyglucose F18; D011092:Polyethylene Glycols; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human
Breast cancer; HER-2 positive; Liposomal anthracycline; Neoadjuvant chemotherapy; Pathologic complete response; Trastuzumab