Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study.
OBJECTIVE
TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor-copositive metastatic breast cancer (MBC).


METHODS
Postmenopausal women with HER2/hormone receptor-copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor-positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure.


CONCLUSIONS
Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor-copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.
Kaufman
Bella
B
Chaim Sheba Medical Center, Tel Hashomer, Israel. bella.kaufman@sheba.health.gov.il
Mackey
John R
JR
Clemens
Michael R
MR
Bapsy
Poonamalle P
PP
Vaid
Ashok
A
Wardley
Andrew
A
Tjulandin
Sergei
S
Jahn
Michaela
M
Lehle
Michaela
M
Feyereislova
Andrea
A
Révil
Cédric
C
Jones
Alison
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D017698:Postmenopause / Q000187:drug effects; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood; D011960:Receptors, Estrogen / Q000097:blood; D011980:Receptors, Progesterone / Q000097:blood; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
D000077384:Anastrozole; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; D014230:Triazoles