Plasma EGFR mutation cfDNA predicts advanced lung cancer outcome

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By Lynda Williams, Senior medwireNews Reporter

Monitoring plasma cell-free (cf)DNA levels of epidermal growth factor receptor (EGFR) mutations may indicate prognosis for patients with lung adenocarcinoma after EGFR–tyrosine kinase inhibitor (TKI) therapy, research suggests.

Gee-Chen Chang, from National Yang-Ming University in Taipei, Taiwan, and team compared serial tumour and plasma cfDNA samples taken from 72 lung cancer patients, 86.1% of whom had exon 19 deletions or L858R mutations.

Using the peptide nucleic acid-Zip nucleic acid polymerase chain reaction clamp technique, the team showed that pretreatment plasma samples were 59.7% sensitive and 100.0% specific for the detection of EGFR mutations.

And the test’s sensitivity increased with disease stage, from 23.8% in patients with stage IIIb and IV-M1a compared with 78.0% for those with stage IV-M1b disease, the team reports in the Journal of Thoracic Oncology.

All 62 mutation-positive patients were treated with the EGFR–TKIs gefitinib or erlotinib; the objective response rate was 74.2% and the disease control rate 82.3%. The patients had median progression-free and overall survival times of 8.8 and 20.5 months, respectively.

All EGFR mutation-negative patients at baseline tested negative at the 10-week check-point, as did 75.7% of the 37 patients who had originally tested positive. Nine (24.3%) patients continued to test positive for EGFR mutations in their plasma cfDNA at follow-up.

Compared with patients who cleared EGFR mutations from their plasma, patients who continued to test positive for EGFR cfDNA were 5.26 times more likely to have a poorer disease control rate, the researchers say.

Moreover, patients who retained EGFR mutations in their plasma were 1.97 times more likely to have shorter progression-free survival and 1.82 times more likely to have shorter overall survival than those who no longer had EGFR mutations in their plasma.

“[O]ur study demonstrated that dynamic changes in plasma EGFR mutation status can serve as an independent predictor of patients’ outcome and be used to help identify patients at risk of rapid disease progression”, Chang et al conclude.

“Further studies are warranted to determine how to adjust the treatments according to dynamic status of plasma EGFR mutations.”

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