Abstract
IntroductionThe potential of oncogene-driven targeted therapy is perhaps most fully realized in non-small cell lung cancer (NSCLC), given the number of genomic targets and approved matched therapies. However, invasive tissue biopsy at the time of each disease progression may not be possible and is associated with high morbidity and cost. Use of newly available “liquid biopsies” can circumvent these issues.Results83% of subjects had at least one genomic alteration identified in plasma. Most commonly mutated genes were TP53, KRAS and EGFR. Subjects with no detectable ctDNA were more likely to have small volume disease, lepidic growth pattern, mucinous tumors or isolated leptomeningeal disease.MethodsSubjects were individuals with NSCLC undergoing analysis of cell-free circulating tumor DNA using a validated, commercially-available next-generation sequencing assay at a single institution. Demographic, clinicopathologic information and results from tissue and plasma-based genomic testing were reviewed for each subject.ConclusionsThis is the first clinic-based series of NSCLC patients assessing outcomes of targeted therapies using a commercially available ctDNA assay. Over 80% of patients had detectable ctDNA, concordance between paired tissue and blood for truncal oncogenic drivers was high and patients with biomarkers identified in plasma had PFS in the expected range. These data suggest that biopsy-free ctDNA analysis is a viable first choice when the diagnostic tissue biopsy is insufficient for genotyping or at the time of progression when a repeated invasive tissue biopsy is not possible/preferred.
Highlights
The potential of oncogene-driven targeted therapy is perhaps most fully realized in non-small cell lung cancer (NSCLC), given the number of genomic targets and approved matched therapies
Over 80% of patients had detectable circulating tumor DNA (ctDNA), concordance between paired tissue and blood for truncal oncogenic drivers was high and patients with biomarkers identified in plasma had PFS in the expected range
These data suggest that biopsy-free ctDNA analysis is a viable first choice when the diagnostic tissue biopsy is insufficient for genotyping or at the time of progression when a repeated invasive tissue biopsy is not possible/preferred
Summary
The potential of oncogene-driven targeted therapy is perhaps most fully realized in non-small cell lung cancer (NSCLC), given the number of genomic targets and approved matched therapies. Genomic profiling of tumor DNA to identify targetable oncogenic drivers is rapidly becoming a part of standard care for many different cancer types [1] Targeted therapy of these mutations can result in dramatic and immediate responses and imparting median progression-free survival intervals 2–3 times longer than in patients receiving standard chemotherapy. The vast majority of these patients will recur or progress on treatment, the availability of 2nd and 3rd generation targeted therapies for emerging resistance mutations in EGFR and ALK fusion driven lung cancer has prolonged intervals of disease-free survival [2, 3], leading to recommendations to repeat biopsies for genotyping lung cancer patients progressing after first line targeted therapies. Emerging genomic targets in NSCLC include alterations in AXL, NTRK and others [6,7,8] the convergent genomic evolution of lung cancer is relatively well characterized, which has allowed for the recent development of second and third generation targeted therapies to overcome acquired resistance [9]
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