Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).
BACKGROUND
Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer. In this study, we compared 12 versus 6 months of adjuvant trastuzumab.


METHODS
Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were randomized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense, granulocyte colony-stimulating factor (G-CSF)-supported docetaxel (75 mg/m(2) every 14 days for four cycles). All patients received upfront dose-dense, G-CSF-supported FEC (5-fluorouracil 700 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 700 mg/m(2) every 14 days for four cycles). Randomization was carried out before commence of chemotherapy. The primary end point was the 3-year disease-free survival (DFS).


RESULTS
A total of 481 patients were randomized to receive 12 months (n = 241) or 6 months (n = 240) of adjuvant trastuzumab. Chemotherapy was completed in 99% and 98% of patients, while trastuzumab therapy in 100% and 96% of patients in the 12- and 6-month groups, respectively. After 47 and 51 months of median follow-up, there were 17 (7.1%) and 28 (11.7%) disease relapses in the 12- and 6-month groups (P = 0.08). The 3-year DFS was 95.7% versus 93.3% in favor of the 12-month treatment group (hazard ratio = 1.57; 95% confidence interval 0.86-2.10; P = 0.137). There was no difference in terms of overall survival and cardiac toxicity between the two groups.


CONCLUSIONS
Our study failed to show noninferiority for the 6-month arm. The results further support the current standard of care that is administration of adjuvant trastuzumab for 12 months.
Department of Medical Oncology, University General Hospital of Heraklion, Heraklion medoncsec@med.uoc.gr.
D
D
Mavroudis
Oncology Unit, General Hospital of Heraklion 'Venizelio'
E
E
Saloustros
Department of Medical Oncology, Elena Venizelou Hospital, Athens.
N
N
Malamos
Department of Medical Oncology, University General Hospital of Alexandroupolis, Alexandroupolis.
S
S
Kakolyris
Department of Medical Oncology, Bioklinic of Thessaloniki, Thessaloniki.
I
I
Boukovinas
Department of Medical Oncology, Theageneio Hospital, Thessaloniki.
P
P
Papakotoulas
Department of Medical Oncology, 251 Airforce General Hospital, Athens.
N
N
Kentepozidis
Department of Medical Oncology, Metaxa Hospital, Athens.
N
N
Ziras
Department of Medical Oncology, University of Crete, School of Medicine, Heraklion, Greece.
V
V
Georgoulias
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D000068878:Trastuzumab / Q000008:administration & dosage; D055815:Young Adult
D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human
6 months; adjuvant; breast cancer; randomized; trastuzumab