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

Ian E. Krop, Patricia LoRusso, Kathy Miller, Shanu Modi, Denise Yardley, Gladys Rodriguez, Ellie Guardino, Michael Lu, Maoxia Zheng, Sandhya Girish, Lukas Amler, Eric P. Winer, Hope S. Rugo

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Abstract

Purpose: 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. Patients and 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%). Conclusion: 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.

Original languageEnglish
Pages (from-to)3234-3241
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number26
DOIs
StatePublished - Sep 10 2012

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Anthracyclines
Breast Neoplasms
Disease-Free Survival
Cellulitis
Therapeutics
Trastuzumab
human ERBB2 protein
lapatinib
ado-trastuzumab emtansine
Capecitabine
taxane
Thrombocytopenia
Fatigue
Safety
Drug Therapy
Antibodies
Pharmaceutical Preparations
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Krop, Ian E.; LoRusso, Patricia; Miller, Kathy; Modi, Shanu; Yardley, Denise; Rodriguez, Gladys; Guardino, Ellie; Lu, Michael; Zheng, Maoxia; Girish, Sandhya; Amler, Lukas; Winer, Eric P.; Rugo, Hope S.

In: Journal of Clinical Oncology, Vol. 30, No. 26, 10.09.2012, p. 3234-3241.

Research output: Contribution to journalArticle

Krop, Ian E. ; LoRusso, Patricia ; Miller, Kathy ; Modi, Shanu ; Yardley, Denise ; Rodriguez, Gladys ; Guardino, Ellie ; Lu, Michael ; Zheng, Maoxia ; Girish, Sandhya ; Amler, Lukas ; Winer, Eric P. ; Rugo, Hope S. / 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. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 26. pp. 3234-3241.
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title = "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",
abstract = "Purpose: 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. Patients and 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{\%}). Conclusion: 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.",
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AU - Krop, Ian E.

AU - LoRusso, Patricia

AU - Miller, Kathy

AU - Modi, Shanu

AU - Yardley, Denise

AU - Rodriguez, Gladys

AU - Guardino, Ellie

AU - Lu, Michael

AU - Zheng, Maoxia

AU - Girish, Sandhya

AU - Amler, Lukas

AU - Winer, Eric P.

AU - Rugo, Hope S.

PY - 2012/9/10

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N2 - Purpose: 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. Patients and 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%). Conclusion: 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.

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