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Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.

ABSTRACT: The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC. Nevertheless, IOs are active only in a subgroup of patients and biomarkers for appropriate patients' selection are urgently needed to offer the patients an effective therapy, and also to manage the costs. Tumor mutation burden (TMB) has powerfully emerged as a potential biomarker for immunotherapy and might enter the clinic in the next months, although different challenges are still unsolved. Different methods exist to evaluate TMB in tissue, ranging from whole exome sequencing (WES) to targeted sequencing of smaller sets of genes, which need to be fully standardized to ensure that patients receive an appropriate TMB test with clear clinical interpretation. In addition, as already happened for the implementation of liquid biopsy testing from NSCLC patients to identify targetable alterations, researchers are also evaluating the possibility to calculate TMB in blood, to further enlarge the number of NSCLC patients who may benefit from immunotherapy. Preliminary data highlight the difficulty to develop targeted sequencing panels for the assessment of TMB starting from the circulating cell free DNA (cfDNA). The applicability of TMB testing on liquid biopsy needs further investigation and may be clarified within the ongoing clinical trials.

SUBMITTER: Fenizia F

PROVIDER: S-EPMC6249618 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.

Fenizia Francesca F Pasquale Raffaella R Roma Cristin C Bergantino Francesca F Iannaccone Alessia A Normanno Nicola N

Translational lung cancer research 20181201 6

The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC. Nevertheless, IOs are active on ...[more]

PMID: 30505711

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Project description:15-40% of non-small cell lung cancer (NSCLC) patients harbor epidermal growth factor receptor (EGFR)-sensitizing mutations. Tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in this population, yet all patients will ultimately progress. Liquid biopsy can reliably identify somatic tumor-associated EGFR mutations in plasma. This study aimed to assess the feasibility and value of the quantitative assessment of EGFR driver mutations in plasma in EGFR-mutated NSCLC patients treated with EGFR-TKIs as a tool to evaluate therapeutic response to TKIs and monitor for disease progression. The study included 136 patients with tissue biopsy-confirmed EGFR-sensitizing, mutation-positive lung adenocarcinoma with plasma collected prior to TKI treatment and at least two post-initiation TKI treatment/follow-up blood samples. Plasma samples were tested with the cobas® EGFR Mutation Test v2 (cobas EGFR Test), and semi-quantitative index (SQI) values for each identified mutation were reported by the assay software. The most common baseline EGFR mutations detected in tissue were L858R (53.7%) and exon 19 deletion (39.7%). Plasma cell-free DNA analysis detected EGFR mutations in 74% of the baseline samples. Objective response rate by RECIST 1.1 was achieved in 72% of patients, while 93% had a molecular response (defined as disappearance of the EGFR mutation from plasma). 83% of patients had molecular progression (MP; 1.5X SQI increase or new T790M mutation), and 82% who had a clinical response had clinical progression. On average, MP occurred 42 days prior to clinical progression. Patients who progressed while on first-line TKI showed MP of the original EGFR-sensitizing mutations prior to the emergence of a T790M mutation, which was detected in 27% of the EGFR plasma-positive patients. Longitudinal monitoring of EGFR mutational load in plasma is feasible and can predict both response and clinical progression in EGFR-mutated NSCLC patients treated with EGFR-TKIs, as well as detect treatment-emergent EGFR mutations.

Dataset Information

Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.

Publications

Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.

Similar Datasets

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