Search results for " TKI"
showing 7 items of 7 documents
Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors following progression with imatinib, sunitinib and regorafenib
2018
Background: Rechallenge with imatinib is an option in advanced gastrointestinal stromal tumor (GIST) patients following progression with standard tyrosine-kinase inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively collected data from metastatic Italian GIST patients treated with imatinib resumption after progression to conventional TKIs. Methods: A total of 104 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected from six referral Italian institutions. Mutational analysis was recorded and correlated with survival and response according to RECIST 1.1 or CHOI criteria. Results: Overall, 71 patients treated with ima…
Detection and clinical implications of a novel BCR-ABL1 E12A2 insertion/deletion in a CML patient expressing the E13A2 isoform
2019
Background/Aim: The Philadelphia chromosome is the most frequent cytogenetic abnormality in chronic myelogenous (CML). More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement. Furthermore, about 5% of CML patients are diagnosed with rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. However, there is limited evidence concerning the clinical and prognostic implications of these infrequent oncogenic variants for CML patients receiving tyrosine kinase inhibitors (TKIs). Case Report: We describe a novel atypical e12a2 insertion/deletion (In…
EGFR inhibition in NSCLC: New findings…. and opened questions?
2017
The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent f…
The role of microRNAs in driving EGFR-TKI resistance in NSCLC cell lines
2016
Background: the inhibition of EGFR kinase activity by tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, can result in improved response and prolonged progression-free survival (PFS) in NSCLC patients harboring sensitizing exon 19del and exon 21 L858R mutations. Unfortunately, almost all patients will develop resistance to EGFR-TKI, in particular T790M is the most frequent mutation. Nowadays, new methods are urgently needed for a rapid, cost-effective and non-invasive identification of biomarkers as a valuable tool for obtaining the genetic follow-up data during the course of the disease. Circulating microRNAs might represent a new precious biomarker for patients’ moni…
Upfront radiation versus EGFR-TKI : which is the best approach for EGFR-mutated NSCLC patients with brain metastasis?
2017
In The Journal of Clinical Oncology , William J. Magnuson (1) and colleagues have recently reported the results of a multicenter retrospective analysis comparing the impact of three different treatment strategies on survival outcomes of 351 patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) and brain metastases (BM). Treatment options included stereotactic radiosurgery (SRS) followed by EGFR-TKI (n=100), whole-brain radiotherapy (WBRT) followed by EGFR-TKI (n=120), or EGFR-TKI followed by SRS or WBRT at the time of intracranial progression (n=131). Results showed a significantly longer median overall survival (OS) in patients who received upfron…
Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost–effectiveness analysis
2019
Aim: Osimertinib improves progression-free survival in first-line EGFR mutation–positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost–effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR–TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR–TKIs. An incremental cost–effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimerti…
Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
2014
Abstract: Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current…