A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine.
OBJECTIVE
To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies.


METHODS
In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety.


RESULTS
Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%).


CONCLUSIONS
T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.
Dana-Farber Cancer Institute, 450 Brookline Ave, Boston MA 02215, USA. ikrop@partners.org
Ian E
IE
Krop
Patricia
P
LoRusso
Kathy D
KD
Miller
Shanu
S
Modi
Denise
D
Yardley
Gladys
G
Rodriguez
Ellie
E
Guardino
Michael
M
Lu
Maoxia
M
Zheng
Sandhya
S
Girish
Lukas
L
Amler
Eric P
EP
Winer
Hope S
HS
Rugo
D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D000077341:Lapatinib; D008297:Male; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab
D000080044:Ado-Trastuzumab Emtansine; D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000922:Immunotoxins; D000077341:Lapatinib; D008453:Maytansine; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C080625:taxane