title: Lapatinib-associated mucocutaneous toxicities are clinical predictors of improved progression-free survival in patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer.
abstract: This study is aimed to identify clinical predictors, other than HER2 overexpression, for the response to lapatinib plus capecitabine (LAPCAP) in patients with HER2-positive advanced breast cancer (HER2ABC). Data from our medical records of 76 patients from June 2009 to March 2013 were analyzed. Evaluations of these patients with HER2ABC treated with LAPCAP included baseline characteristics, dose modifications, efficacy, and incidence of adverse events (AEs). With a median follow-up of 20 months, the median number of prior therapies for ABC before LAPCAP was 2 (range 0-13), and 66 patients had previously received trastuzumab. For LAPCAP, the overall response rate was 21 %, and the clinical benefit rate was 60 %. During the initial 12-month observation period, 93 % of patients had AEs. The most common AE was hand-foot syndrome (HFS) in 55 patients. Progression-free survival (PFS) was better in patients who had HFS than in those who did not (p = 0.0002). Since HFS is a well-known AE associated with CAP, whether CAP dose affected PFS or not was investigated, but no positive relationship was found. Since several studies with EGFR-targeted agents have suggested a positive correlation between cutaneous toxicities and outcomes, whether the incidence of any AEs affected PFS or not was explored among 76 patients. HFS, diarrhea, and rash were significant favorable factors (p = 0.0002, 0.0088, and 0.0011). The median PFS of patients who had all three AEs was 13.2 months, compared with 2.6 months for those who did not (p = 0.00000174). Mucocutaneous toxicities may be predictors of the response to LAP in patients with HER2ABC.
authors.affiliation: Beast Medical Oncology, Breast Oncology Center, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan, kazuhiro.araki@jfcr.or.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Araki
authors.forename: Ippei
authors.initials: I
authors.lastname: Fukada
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced*; D018572:Disease-Free Survival; D003875:Drug Eruptions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases; D012189:Retrospective Studies
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases