MET inhibitors have shown activity in non-small cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect and thus response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with Next Generation Sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with METΔex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally co-exist with other drivers. For METΔex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies.
antihypertensives class, 184 for M04-gout preparations, 135 for C10-lipid modifying agents and 218 for B03-antianaemic preparations. 64% of patients (139) used gastroprotectors, especially proton pump inhibitors (PPIs). 3 DDIs, of 289 detected, were considered contraindicated and potentially serious, and were due to antipsychotic drugs. Drugs most responsible for DDIs were: cardioaspirin, PPIs, angiotensin receptor blockers and diuretics. 975 (4.2±2.2 per patient) and 571 (2.4±1.7 per patient) inappropriate drugs were identified according to STOPP criteria and Beers criteria, respectively. Conclusion and relevance Polypharmacy is associated with a high incidence of DDIs and an increased risk of mortality and hospitalisation. The use of the ICT tool and the clinical pharmacist who bring their contribution in terms of pharmacological and pharmacokinetic knowledge have significantly contributed to the improvement in prescriptive appropriateness and minimised the risk of adverse events. REFERENCES AND/OR ACKNOWLEDGEMENTS 1. Critical analysis of the information and communication technologies' (ICT) tools most used in clinical practice by the pharmacist. Masucci S, Cerutti E, Riba M, Gasco AL (EAHP Congress 2019).
Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, METΔex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69–2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39–0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12–1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care.
Background: Collecting duct carcinoma of the kidney (CDC) is a rare cancer associated with bad prognosis and, at present, with no specific effective therapies. Case Report: We report a clinical case with disseminated highgrade CDC presenting with widespread metastasis to both lungs, pelvic bones, axial skeleton, and the central nervous system (posterior fossa, both hemispheres and pituitary-hypothalamic). The primary tumor in the kidney was demonstrated (by fluorescence in situ hybridization and immunohistochemistry with Herceptest (3+ score)) to significantly overexpress HER2. Critically ill at presentation, the patient received oral capecitabine together with double HER2 blockade with both intravenous trastuzumab and oral lapatinib. His clinical response was a dramatic improvement and a progressive decline in the radiological size of all of his multiple cancer lesions. Conclusion: Double HER2 blockade is an effective therapy in disseminated CDC even in the presence of brain metastases.
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