title: RC0639: phase II study of paclitaxel, trastuzumab, and lapatinib as adjuvant therapy for early stage HER2-positive breast cancer.
abstract: Lapatinib adds to the efficacy of trastuzumab in preclinical models and also in the neo-adjuvant setting. This study assesses the safety and feasibility of adding lapatinib to paclitaxel and trastuzumab (THL) as part of the adjuvant therapy for HER2-positive breast cancer (HER2+ BC). In this single-arm phase II study, patients with stages I-III HER2+ BC received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. The primary endpoint was symptomatic congestive heart failure, secondary endpoints included overall safety. A total of 109 eligible patients were enrolled. Median follow-up is 4.3 years. No patients experienced congestive heart failure while on treatment. Mean left ventricular ejection fraction at baseline and at the end of THL were 63.6 % (N = 109, SD = 5.7) and 59.8 % (N = 98, SD = 8.1), respectively [mean change -3.95 % (N = 98, SD = 8.3), p < 0.001]. One hundred and two patients initiated post-AC treatment; of them, 31 % experienced grade 3 (no G4) diarrhea with lapatinib at 750 mg/day. The addition of lapatinib to paclitaxel and trastuzumab following AC does not add cardiac toxicity. Lapatinib dose of 750 mg/day in combination with standard chemotherapy plus trastuzumab has acceptable overall tolerability.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd. S., Jacksonville, FL, 32224, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Moreno-Aspitia
authors.forename: Amylou C
authors.initials: AC
authors.lastname: Dueck
authors.forename: Ismael
authors.initials: I
authors.lastname: Ghanem-Cañete
authors.forename: Tejal
authors.initials: T
authors.lastname: Patel
authors.forename: Shaker
authors.initials: S
authors.lastname: Dakhil
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Sandra
authors.initials: S
authors.lastname: Franco
authors.forename: Stephen
authors.initials: S
authors.lastname: Kahanic
authors.forename: Gerardo
authors.initials: G
authors.lastname: Colon-Otero
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Tenner
authors.forename: Richard
authors.initials: R
authors.lastname: Rodeheffer
authors.forename: Ann E
authors.initials: AE
authors.lastname: McCullough
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Frances M
authors.initials: FM
authors.lastname: Palmieri
authors.forename: Donald
authors.initials: D
authors.lastname: Northfelt
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects; D000068878:Trastuzumab; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human