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Lung cancer represents the most common cause of cancer related deaths worldwide and it is particularly difficult to biopsy with more than 25% of invasive biopsies failing. In recent years, there has been a dramatic improvement in the outcome of some lung cancer patients thanks to treatment with tyrosine kinase inhibitors (TKI) such as Erlotinib or Gefitinib that target EGFR, a gene commonly mutated in this disease.

Non-small cell lung carcinoma (NSCLC) accounts for approximately 85% of all lung cancers and mutations in the EGFR gene are present in 18% of patients, increasing to ~50% in patients of Asian descent. Nearly 90% of mutations are either the L858R mutation or deletions of exon 19 and are non-overlapping with other mutations (i.e. KRAS mutations, ALK rearrangements, etc.). The use of drugs such as Gefitinib (Iressa®), Erlotinib (Tarceva®) and Afatinib (Giotrif®) has dramatically improved the outcome for NSCLC patients from a median OS <12 months with conventional chemotherapy, to a median OS of 2-3 years. The presence of EGFR mutations are FDA and EMA-approved companion biomarkers for the use of these drugs. As a consequence EGFR mutation testing is recommended for all patients with advanced NSCLC (60-75% of patients at diagnosis).



In 2016, the FDA approved use of liquid biopsies for EGFR testing in NSCLC cases with insufficient biopsy material.

Monitoring TKIs resistance: EGFR T790M mutation

Despite the fact that TKI-based therapy has greatly improved the outcome for NSCLC patients, unfortunately most patients will develop resistance to further treatment about 12-18 months later. Although resistance can have many origins, in most cases resistance is associated with the appearance of the T790M EGFR mutation. Clinical trials have demonstrated that >60% of T790M-mutated patients respond to third-generation selective TKIs such as Osimertinib (Tagrisso®) (AstraZeneca). As a consequence, the FDA granted accelerated approval to this drug in November 2015 (in EU in Feb 2016), when used in association with an approved companion diagnostic to detect T790M-positive NSCLC patients (i.e. Cobas® and Therascreen®).

Current clinical standards consider testing EGFR T790M mutation in NSCLC EGFR-positive patients receiving TKIs when there are clear signs of disease progression. If the result is positive in liquid biopsy, the patient will get Osimertinib as a third-line treatment. If the result is negative in liquid biopsy and the re-biopsy is unavailable, the patient will go back to cytotoxic chemotherapy treatment.

We are developing the Indicate device to detect the L858R and T790M mutations of EGFR, before expanding the technology to other actionable mutations