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| |  Gene Mutations Predict Response to Treatment With Tyrosine Kinase Inhibitors in Patients With Advanced NSCLC: Presented at EMCTO By Jenny Powers LUGANO, Switzerland -- May 6, 2009 -- Epidermal growth factor receptor (EGFR) gene mutations have been found to be a significant predictor of sensitivity to treatment with tyrosine kinase inhibitor (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC), according to research presented here at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2009. Lucio Crinò, MD, Oncohematology Perugia, Perugia, Italy, and colleagues reported results of their study here on May 2. Patients with advanced NSCLC who had been treated with TKIs (gefitinib or erlotinib) after failure of first- or second-line platinum-based chemotherapy were examined for EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) gene mutations to determine the clinical implication of these mutations in relation to TKI treatment. Genomic DNA was isolated from 128 TKI-treated patients. The DNA was amplified by nested polymer chain reaction for EGFR (exons 18, 19, 20, and 21), PIK3CA (exons 9 and 20) and KRAS (exon 2), and sequenced in both sense and antisense directions. The response to TKI treatment was measured by Response Evaluation Criteria in Solid Tumors criteria. Baseline patient characteristics were similar between the treatment groups. EGFR mutations were detected in 25.4% of treated patients; deletional mutations in exon 19 occurred in 16.4% of patients; point mutations in exon 20 were detected in 4.7% of patients and in exon 21 in 4.7% of patients. Mutations in KRAS and PIK3CA were found in 5.7% and 2.7% of patients, respectively. The response rate to TKIs in patients with EGFR mutations was 58.4% compared with 19.7% in patients without EGFR mutations (P = .001), with a disease-control rate of 74.2% versus 49.4% (P = .02), respectively. The median time to progression was 8 months versus 3 months for patients with EGFR mutations compared with patients without EGFR mutations (P = .06). The overall survival rate was similar in all patients, but of 25 patients with TKI-sensitive EGFR mutations (deletion in exon 19, missense L858R), a significantly longer time to progression was observed (median 8 months in patients with mutations vs 3 months in those without [P = .008]), as well as a better overall survival rate (median not reached in those with mutations vs 11 months in those without [P = .07]). Patients with EGFR mutations had an 88% response rate, and the time to progression was significantly better (P = .03). Patients with KRAS mutations responded differently in all respects to treatment with TKIs compared with patients having PIK3CA mutations. The authors confirmed that EGFR mutations (deletion in exon 19, missense L858R) are a significant predictor of sensitivity to TKI treatment. They further concluded that evaluation of KRAS and PIK3CA mutations could contribute to the identification of lung-cancer patients who would benefit from treatment with TKIs. EMCTO 2009 was co-organised by the European Society for Medical Oncology (ESMO), the European Society for Therapeutic Radiology and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS), and the European Respiratory Society (ERS).
[Presentation title: EGFR, KRAS, PIK3CA Mutations and Response to Tyrosine Kinase Inhibitors (TKIS) in Advanced NSCLC Patients. Abstract 128PD]
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