Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer: A Phase Ib Study.

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  • Additional Information
    • Source:
      Publisher: Karger Country of Publication: Switzerland NLM ID: 0135054 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1423-0232 (Electronic) Linking ISSN: 00302414 NLM ISO Abbreviation: Oncology Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, New York, Karger.
    • Subject Terms:
      Breast Neoplasms/*drug therapy ; Maytansine/*analogs & derivatives ; Oxonic Acid/*administration & dosage ; Tegafur/*administration & dosage ; Trastuzumab/*administration & dosage; Ado-Trastuzumab Emtansine ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/genetics ; Drug Combinations ; Female ; Humans ; Maytansine/administration & dosage ; Maytansine/adverse effects ; Middle Aged ; Neoplasm Metastasis ; Oxonic Acid/adverse effects ; Receptor, ErbB-2/genetics ; Tegafur/adverse effects ; Trastuzumab/adverse effects ; Treatment Outcome
    • Abstract:
      Background: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer.
      Objectives: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed.
      Methods: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment.
      Results: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1.
      Conclusions: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.
      (© 2019 S. Karger AG, Basel.)
    • Contributed Indexing:
      Keywords: Chemotherapy; Human epidermal growth factor receptor 2; Metastatic breast cancer; Phase I study; S-1
    • Accession Number:
      0 (Drug Combinations)
      14083FR882 (Maytansine)
      150863-82-4 (S 1 (combination))
      1548R74NSZ (Tegafur)
      5VT6420TIG (Oxonic Acid)
      EC 2.7.10.1 (ERBB2 protein, human)
      EC 2.7.10.1 (Receptor, ErbB-2)
      P188ANX8CK (Trastuzumab)
      SE2KH7T06F (Ado-Trastuzumab Emtansine)
    • Publication Date:
      Date Created: 20190321 Date Completed: 20190617 Latest Revision: 20191210
    • Publication Date:
      20231215
    • Accession Number:
      10.1159/000497276
    • Accession Number:
      30893699