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The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report.
The increase in activating EGFR mutation in plasma is an early biomarker to monitor response to osimertinib: a case report.
- Source :
-
BMC cancer [BMC Cancer] 2019 Apr 30; Vol. 19 (1), pp. 410. Date of Electronic Publication: 2019 Apr 30. - Publication Year :
- 2019
-
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.<br />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.<br />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.
- Subjects :
- Acrylamides therapeutic use
Aniline Compounds therapeutic use
Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung genetics
Disease Progression
ErbB Receptors blood
ErbB Receptors genetics
Female
Gene Amplification
Humans
Lung Neoplasms blood
Lung Neoplasms genetics
Middle Aged
Proto-Oncogene Proteins c-met genetics
Treatment Outcome
Acrylamides administration & dosage
Aniline Compounds administration & dosage
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Sequence Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31039766
- Full Text :
- https://doi.org/10.1186/s12885-019-5604-6