title: Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.
abstract: Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.).
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan. hrmukai@east.ncc.go.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mukai
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.affiliation: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsubara
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.affiliation: Department of Breast Oncology, Saitama Medical University International Medical Center, Hidaka, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Fumikata
authors.initials: F
authors.lastname: Hara
authors.affiliation: Oncology Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ohwada
authors.affiliation: Institute of Molecular Oncology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yasutsuna
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000080908:Broadly Neutralizing Antibodies; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D014408:Biomarkers, Tumor; D000080908:Broadly Neutralizing Antibodies; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C585471:patritumab
keywords: Breast cancer; HER3 protein; human; metastasis; patritumab; trastuzumab