Liquid re-biopsy has become an acceptable alternative to tumor re-biopsy to identify acquired T790M mutation after tyrosine-kinase inhibitors with or without subsequent chemotherapy for metastatic EGFR-mutated NSCLC. We prospectively investigated if there were any predictors for development of acquired T790M mutation in plasma DNA.
Patients with tumour-biopsy proven activating EGFR mutations who received 1st line TKI with or without subsequent lines of TKI and/or chemotherapy after failure to 1st line TKI were prospectively recruited. Blood (10ml ETDA) was taken for plasma DNA for the detection of T790M mutation at the time of progressive disease to TKI with or without subsequent TKI/chemotherapy. Univariable and multivariable logistic regression was performed for clinical and molecular predictors for presence of T790M mutation.
68 patients received TKI alone with or without further TKI/chemotherapy before liquid re-biopsy at the time of progressive disease. 19 (51.4%) patients with initial exon 19 deletion versus 8 (25.8%) patients with initial exon 21 mutation developed T790M on liquid re-biopsy (p = 0.032). Univariable analysis showed that age ≥75 years (OR 4.15, 95% CI 1.06-16.21, p = 0.041), ≥2 sites of distant metastases before 1st line TKI (OR 13.51, 95% CI 1.65-111.11 p = 0.015) and exon 19 deletion (vs. exon 21 mutations) (OR 3.04, 95% CI 1.08-8.51, p = 0.035) were significant predictive factors, while multivariable analysis showed that ≥2 sites of distant metastases (OR 13.70, 95% CI 1.64-111.11, p = 0.001) and exon 19 deletion (OR 3.09, 95% CI 1.03-9.29, p = 0.039) were independent predictive factors of development of T790M mutation. Use of chemotherapy and use of more than 1 line of TKI were not predictors.
Targeted patient subgroups were identified for the development of T790M mutation after 1st line TKI and/or subsequent TKI/chemotherapy, which were important to guide subsequent management.
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Department of Clinical Oncology, The University of Hong Kong
All authors have declared no conflicts of interest.