Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial.
BACKGROUND
The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers.


METHODS
Patients with stages I-III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers.


RESULTS
We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0-66.2%) for EC-DT and 25.5% (95% CI:13.5-37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3-4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups.


CONCLUSIONS
EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR.
Department of Medical Oncology, Hospital Universitario Virgen de la Victoria, Málaga 29010, Spain.
E
E
Alba
Hospital Parc de Salut Mar, 8003 Barcelona, Spain.
J
J
Albanell
Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
J
J
de la Haba
Hospital Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, 8041 Barcelona, Spain.
A
A
Barnadas
Complejo Hospitalario Universitario de A Coruña, 15006A Coruña, Spain.
L
L
Calvo
Hospital General de Jaén, 23007 Jaén, Spain.
P
P
Sánchez-Rovira
Centro Oncológico de Galicia, 15009A Coruña, Spain.
M
M
Ramos
1] Hospital Parc de Salut Mar, 8003 Barcelona, Spain [2] Department of Pathology, Fundación Jiménez Díaz, 28040 Madrid, Spain.
F
F
Rojo
Department of Pathology and Oncology, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain.
O
O
Burgués
GEICAM (Spanish Breast Cancer Research Group), 28703 Madrid, Spain.
E
E
Carrasco
GEICAM (Spanish Breast Cancer Research Group), 28703 Madrid, Spain.
R
R
Caballero
Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
I
I
Porras
Hospital Santa Creu i Sant Pau, Universidad Autónoma de Barcelona, 8041 Barcelona, Spain.
A
A
Tibau
GEICAM (Spanish Breast Cancer Research Group), 28703 Madrid, Spain.
M C
MC
Cámara
Department of Pathology and Oncology, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain.
A
A
Lluch
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human