Early prediction of resistance to tyrosine kinase inhibitors in NSCLC

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A study published in the journal Oncotarget has reported that at clinical progression, 64 EGFR T790M plasma positive patients were subjected to second line-treatment with osimertinib and strictly monitored during the first month of therapy.

Plasma analysis by the EGFR Cobas test showed in 57 cases a substantial decrease in the levels of the sensitising EGFR mutant allele, down to a not detectable value.

The research team’s data indicate that plasma monitoring by a simple RT-PCR-based EGFR mutation test in the first month of treatment may be useful for a rapid identification of patients to be subjected to further characterisation by MPS.

Dr Antonio Marchetti from the Laboratory of Diagnostic Molecular Oncology, Center for Advanced Studies and Technology (CAST) and The Department of Medical and Oral Sciences and Biotechnologies at the University of Chieti as well as The Department of Pathology, SS Annunziata Clinical Hospital said: “In non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase-inhibitors (TKIs) therapy, the emergence of acquired resistance can be investigated by plasma monitoring of circulating tumour DNA (ctDNA).”

Several studies have shown a high concordance between the presence of EGFR mutations in tissue and plasma, especially in patients with diffuse metastatic disease.

In a previous study, the authors have shown for the first time that NSCLC patients carrying EGFR mutations in tumour tissue and subjected to first-line treatment with EGFR TKIs, can be strictly monitored in the first days of treatment by repeated blood draws to quantify EGFR mutant alleles in plasma.

These results strongly suggest that the amount of EGFR sensitising mutations in plasma reflects the tumour burden and that the fluctuations in the levels of EGFR sensitising mutations in plasma are closely related to tumour load variations.

However, after a medium period of about 12 months, even patients subjected to second-line treatment with osimertinib, develop resistance with various mechanisms, including EGFR SNV, MET, and HER2 amplification, genetic fusions, etc.

Recently, a series of clinical trials led to the approval of first-line treatment of EGFR-positive NSCLC patients with osimertinib.

The Marchetti Research Team concluded: “Our results indicate that a subset of NSCLC patients subjected to second-line treatment with osimertinib are resistant to treatment due to the presence of different types of mutations. Plasma monitoring by a simple RT-PCR-based EGFR mutation test in the first month of treatment may be useful to rapidly identify these cases and subject them to MPS analysis for further characterisation and treatment.”


Source: Oncotarget / Impact Journals LLC

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The ONA Editor curates oncology news, views and reviews from Australia and around the world for our readers. In aggregated content, original sources will be acknowledged in the article footer.

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