Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.
OBJECTIVE
Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation.


METHODS
Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m(2), both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound.


RESULTS
Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8-31.1, 95% CI 2.7-10.3) and a survival of 18.7 months (1.6-40.8, 95% CI 3.7-33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment.


CONCLUSIONS
Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.
Christodoulou
Christos
C
Second Department of Medical Oncology, Henry Dunant Hospital, Athens, Greece.
Kostopoulos
Ioannis
I
Kalofonos
Haralabos P
HP
Lianos
Evangelos
E
Bobos
Mattheos
M
Briasoulis
Evangelos
E
Gogas
Helen
H
Razis
Evangelia
E
Skarlos
Dimosthenis V
DV
Fountzilas
George
G
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000032:analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011494:Protein Kinases / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab; D016277:Ventricular Function, Left / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D051059:PTEN Phosphohydrolase; D011092:Polyethylene Glycols; D011494:Protein Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D000068878:Trastuzumab; C506643:liposomal doxorubicin; C546842:MTOR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human