martes, 30 de abril de 2019

The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report | BMC Cancer | Full Text

The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report | BMC Cancer | Full Text

BMC Cancer

The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report

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Contributed equally
BMC Cancer201919:410
  • Received: 5 April 2018
  • Accepted: 12 April 2019
  • Published: 
Open Peer Review reports

Abstract

Background

Systemic treatment of advanced non-small cell lung cancer (NSCLC) has changed dramatically since the introduction of targeted therapies. The analysis of circulating tumor DNA (ctDNA) is a valuable approach to monitor the clonal evolution of tumors during treatment with EGFR-tyrosine kinase inhibitors (TKIs) and to detect resistance mutations.

Case presentation

A NSCLC patient with exon 19 deletion (ex19del) of EGFR was treated with osimertinib after multiple lines of treatment and obtained a partial response that lasted over 26 months. Blood was collected at each visit and ctDNA was extracted to monitor ex19del by digital droplet PCR. Within a few weeks from the beginning of osimertinib, ex19del disappeared from plasma but appeared again and steadily increased a few months later anticipating tumor progression. Interestingly, the change in ex19del was much more pronounced than other mutations, since T790M appeared 3 months after the increase of ex19del, and C797S was detectable a few weeks before clinical disease progression. Then the patient received cytotoxic chemotherapy, which was associated with a decrease in ex19del and disappearance of T790M and C797S; however, at disease progression, all EGFR mutations increased again in plasma together with MET amplification which was detected by NGS.

Conclusions

The measurement of ex19del changes in ctDNA is a simple and sensitive approach to monitor clinical outcome to osimertinib and, potentially, to other therapeutic interventions.

Keywords

  • Circulating tumor DNA
  • NSCLC
  • EGFR mutations
  • Treatment monitoring
  • EGFR-TKIs
  • Digital droplet PCR
  • NGS

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