FROM JAMA ONCOLOGY
The type of epidermal growth factor receptor (EGFR) mutation, L858R or exon 19 deletion, detected in either tissue or circulating free DNA, was significantly associated with outcomes in a study of patients with advanced NSCLC, a study has shown.
The findings were published online Feb. 26 in JAMA Oncology.
The results suggest the potential of liquid biopsies or circulating free (cfDNA) as a substitute for tumor biopsy to detect EGFR mutations.
“The amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations,” wrote Dr. Niki Karachaliou and associates (JAMA Oncol. 2015 Feb. 26 [doi:10.1001/jamaoncol.2014.257]).
From 173 patients with oncogenic EGFR mutations (identified by tumor biopsy) enrolled in the EURTAC trial, 97 blood samples were suitable for analysis to detect EGFR mutations in cfDNA, and 76 (78%) EGFR mutations were detected from the blood samples. The investigators developed a novel peptide nucleic acid-mediated PCR assay with 78% sensitivity and 100% specificity, an improvement from sensitivity rates for other methods reported to be below 65%.
Overall, the median OS for the 173 patients enrolled in the EURTAC study was 22.9 months (95% CI, 17.0-30.9) for those in the erlotinib arm vs. 22.1 months (16.5-28.4) for the chemotherapy arm. As in previous study findings, OS for patients with the exon 19 deletion detected in tissue were significantly longer than for those with L858R mutations (25.0 months [18.9-30.9] vs 17.7 [13.5-23.5]; P = .001). In the subset of 97 samples that underwent cfDNA analysis, the OS for those with exon 19 deletions was 30.0 months (19.3-37.7) vs. 13.7 months (7.1-17.7) for L858R mutations (P < .001). Among the 40 samples in the erlotinib arm with EGFR mutations detected in cfDNA, the median OS for exon 19 deletions was 34.4 months (22.9-not reached) vs 13.7 months (2.6-21.9) for L858R mutations (P = .001).
Patients with L858R mutations detected in both tissue and cfDNA had significantly shorter median OS than did those with L858R detected in tissue only (13.7 vs 27.7 months; HR, 2.22; P = .03), reported Dr. Karachaliou of Quiron-Dexeus University Hospital, Barcelona.
For patients in the erlotinib arm, progression-free survival was longer for those with exon 19 deletions than L858R mutations, detected both in tissue and cfDNA. No significant difference in PFS was seen in the chemotherapy arm based on EGFR mutation type.
“The shorter OS – both for all patients and for those receiving erlotinib therapy – observed in the present study among patients with L858R mutations in tissue or cfDNA reinforces this concept of the existence of more than one clinical phenotype of EGFR-mutant NSCLC and suggests that in future analyses, outcomes of patients with exon 19 deletions and those with L858R mutations should not be pooled,” Dr. Karachaliou wrote.
Citing the favorable comparison between their assay and previous methods, the authors concluded that “cfDNA may be a promising method for screening for EGFR mutations in clinical studies, minimizing the need for invasive tumor biopsies.”