Kim, Sung-Bae; Wildiers, Hans; Krop, Ian E; Smitt, Melanie; Yu, Ron; Lysbet de Haas, Sanne; Gonzalez-Martin, Antonio
International journal of cancer
2016Nov ; 139 ( 10 ) :2336-42.
PMID : 27428671
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Kim, Sung-Bae -
Wildiers, Hans -
Krop, Ian E -
Smitt, Melanie -
Yu, Ron -
Lysbet de Haas, Sanne -
Gonzalez-Martin, Antonio -
ABSTRACT
In the phase III TH3RESA study (NCT01419197), 602 patients with HER2-positive advanced breast cancer who received prior taxane therapy and ?? HER2-directed regimens, including trastuzumab and lapatinib (advanced setting), were randomized to trastuzumab emtansine (T-DM1) or treatment of physician's choice (TPC). A statistically significant progression-free survival (PFS) benefit favoring T-DM1 was demonstrated. Here, we examine the relationship between HER2-related biomarkers and PFS in an exploratory analysis. Biomarkers assessed included HER2 (n?=?505) and HER3 (n?=?505) mRNA expression, PIK3CA mutation status (n?=?410) and PTEN protein expression (n?=?358). For biomarkers with continuous data (HER2, HER3, PTEN), subgroups were defined using median values (>median and ?¤median). For all biomarker subgroups, median PFS was longer with T-DM1 vs. TPC. The PFS benefit favoring T-DM1 vs. TPC was numerically greater in the HER2 mRNA >median subgroup (7.2 vs. 3.4 months; unstratified hazard ratio [HR], 0.40; 95% CI, 0.28-0.59; p?median vs. ?¤median. CI - ??2016 UICC.
Antibodies, Monoclonal, Humanized/*therapeutic use; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Biomarkers, Tumor; Breast Neoplasms/*drug therapy/enzymology/*metabolism/pathology; Capecitabine/administration & dosage; Female; Humans; Kaplan-Meier Estimate; Maytansine/*analogs & derivatives/therapeutic use; Phosphatidylinositol 3-Kinases/metabolism; Quinazolines/administration & dosage; Receptor, ErbB-2/*metabolism
MESH
Antibodies, Monoclonal, Humanized/*therapeutic use, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Biomarkers, Tumor, Breast Neoplasms/*drug therapy/enzymology/*metabolism/pathology, Capecitabine/administration & dosage, Female, Humans, Kaplan-Meier Estimate, Maytansine/*analogs & derivatives/therapeutic use, Phosphatidylinositol 3-Kinases/metabolism, Quinazolines/administration & dosage, Receptor, ErbB-2/*metabolism
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