title: FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer.
abstract: On February 22, 2013, the FDA licensed ado-trastuzumab emtansine (Kadcyla; Genentech, Inc.) for use as a single agent for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. The clinical basis for licensure was a phase III trial in 991 patients with HER2-positive MBC that randomly allocated patients to receive ado-trastuzumab emtansine (n=495) or lapatinib in combination with capecitabine (n=496). The coprimary endpoints were progression-free survival (PFS) based on tumor assessments by an independent review committee and overall survival (OS). Statistically significant improvements in PFS and OS were observed in patients receiving ado-trastuzumab emtansine compared with patients receiving lapatinib plus capecitabine [difference in PFS medians of 3.2 months, HR, 0.65 (95% confidence interval, CI, 0.55-0.77), P<0.0001 and difference in OS medians of 5.8 months, HR, 0.68 (95% CI, 0.55-0.85), P=0.0006]. The most common adverse reactions in patients receiving ado-trastuzumab emtansine were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased aminotransferase levels, and constipation. Other significant adverse reactions included hepatobiliary disorders and left ventricular dysfunction. Given the PFS and OS results, the benefit-risk profile was considered favorable.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland. Laleh.AmiriKordestani@fda.hhs.gov.
authors.forename: Laleh
authors.initials: L
authors.lastname: Amiri-Kordestani
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Qiang Casey
authors.initials: QC
authors.lastname: Xu
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Lijun
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authors.lastname: Zhang
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Shenghui W
authors.initials: SW
authors.lastname: Tang
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Linan
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authors.lastname: Ha
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Weinberg
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
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authors.lastname: Chi
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Reyes
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authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
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authors.lastname: Hughes
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Russell
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Sarah Pope
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authors.lastname: Miksinski
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: W David
authors.initials: WD
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authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
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authors.lastname: Palmby
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schrieber
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Qi
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authors.lastname: Liu
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Jian
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authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Pengfei
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authors.lastname: Song
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Nitin
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authors.lastname: Mehrotra
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Lisa
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authors.lastname: Skarupa
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Clouse
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Hakim
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Rajeshwari
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authors.lastname: Sridhara
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amna
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authors.lastname: Ibrahim
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Richard
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authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
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mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human