title: Effect of cardiac dysfunction on treatment outcomes in women receiving trastuzumab for HER2-overexpressing metastatic breast cancer.
abstract: Trastuzumab improves time to disease progression (TTP) and survival when added to chemotherapy for HER-positive metastatic breast cancer (MBC), but it is associated with infrequent cardiac dysfunction (CD). We analyzed data from a previous pivotal randomized trial of 469 women with HER2-overexpressing MBC. The aim was to determine the benefit of adding trastuzumab to chemotherapy in terms of TTP that was free of CD, including all CD, moderate or severe (New York Heart Association class III/IV) CD only, or moderate or severe CD that did not improve with cardiac therapy. We also assessed moderate or severe CD-free survival. We assessed the impact of trastuzumab for these indices on the entire cohort and on specific chemotherapy subsets. Median TTP or any CD improved when trastuzumab was added to all chemotherapy (4.6 months vs. 6.6 months with trastuzumab, P = 0.0001), an anthracycline (doxorubicin or epirubicin) plus cyclophosphamide (AC; 6.0 months vs. 6.6 months, P = 0.24), and paclitaxel (2.8 months vs. 6.6 months, P = 0.0001). When defined as time to moderate or severe CD, median TTP improved when trastuzumab was added to all chemotherapy (4.6 months vs. 7.0 months, P = 0.0001), AC (6.0 months vs. 7.2 months, P = 0.02), and paclitaxel (2.8 months vs. 6.9 months, P = 0.0001). There was no statistical difference between moderate and severe CD-free survival with trastuzumab added to chemotherapy. Outcomes improved with trastuzumab despite CD. In particular, the benefit from trastuzumab/paclitaxel outweighed the potential risk of CD in patients with MBC. These types of analyses will be critical for trials assessing trastuzumab as adjuvant therapy.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, USA. debu.tripathy@utsouthwestern.edu
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Andrew
authors.initials: A
authors.lastname: Seidman
authors.forename: Deborah
authors.initials: D
authors.lastname: Keefe
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Virginia
authors.initials: V
authors.lastname: Paton
authors.forename: Grazyna
authors.initials: G
authors.lastname: Lieberman
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab