Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions.

OBJECTIVES: Imatinib is the first therapeutic option for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Previous studies have shown an improvement in patient survival rates following the use of imatinib. Nevertheless, adequate plasma concentrations of imatinib are necessary to achieve such improvement in survival and limit the toxicity of the drug. This study aims to analyse the influence of imatinib plasma concentrations on efficacy and safety in the treatment of gastrointestinal stromal tumour. MATERIALS AND METHODS: This descriptive, multicentre study analysed plasma levels of imatinib in patients diagnosed with gastrointestinal stromal tumour in the period 2019-2020. An optimal therapeutic range of 750-1500 ng/mL was established for the patient stratification based on their minimum plasma concentrations measured at the steady state. RESULTS: This study included 11 patients with metastatic disease in total, among whom only 54.5% (n = 6) had a minimum plasma concentrations measured at the steady state value within the therapeutic range. A median progression-free survival of 7.0 months was recorded for those patients with minimum plasma concentrations measured at the steady state < 750 ng/mL, while that median progression-free survival value remained unachieved for the group with minimum plasma concentrations measured at the steady state > 750 ng/mL (p = 0.005). The toxicity rate was 25% and 14.3% for patients with minimum plasma concentrations measured at the steady state > 1500 ng/mL and minimum plasma concentrations measured at the steady state ≤1500 ng/mL, respectively (p = 0.66). CONCLUSIONS: The present study aims to describe the correlation between the toxicity and effectiveness of imatinib as a function of minimum plasma concentrations measured at the steady state under routine clinical practice conditions. The results described here show the usefulness of imatinib plasma concentrations monitoring as part of the standard daily routine in our hospitals.

Anti-drug antibodies anti-trastuzumab in the treatment of breast cancer.

INTRODUCTION: Trastuzumab is a monoclonal antibody which could induce the activation of a humoral immune response generating anti-drug antibodies (ADAs). Such response depends of the protein nature and the route of administration (intravenous or subcutaneous). The formation of these antibodies could block the action of trastuzumab (ADA-Tras) and forming immune complexes which decrease its efficacy, so it would be interesting to determine the presence of ADA-Tras in patients treated with trastuzumab. MATERIAL AND METHODS: The blood samples were centrifuged to separate the plasma. The presence of ADA-Tras in plasma was determined using an ELISA-type automated immunoassay. RESULTS: Fifty-one women with non-metastatic HER2-positive breast cancer treated with trastuzumab were included. Two groups were studied: patients treated intravenously and subcutaneously. In neither case was there any presence of ADA-Tras. DISCUSSION: This study may be the first ever conducted under usual clinical practice conditions to detect the presence of ADA-Tras in patients with non-metastatic HER2-positive breast cancer. We have wanted to show the antibodies anti-trastuzumab determination as a possible tool that would enable comparison of potential differences in immunogenic behavior between trastuzumab and its biosimilars.