Liquid biopsy from research to clinical practice: focus on non-small cell lung cancer

ABSTRACT

Introduction

In the current era of personalized medicine, liquid biopsy has acquired a relevant importance in patient management of advanced stage non-small cell lung cancer (NSCLC). As a matter of fact, liquid biopsy may supplant the problem of inadequate tissue for molecular testing. The term ‘liquid biopsy’ refers to a number of different biological fluids, but is most clearly associated with plasma-related platforms. It must be taken into account that pre-analytical processing and the selection of the appropriate technology according to the clinical context may condition the results obtained. In addition, novel clinical applications beyond the evaluation of the molecular status of predictive biomarkers are currently under investigation.

Areas covered

This review summarizes the available evidence on pre-analytical issues and different clinical applications of liquid biopsies in NSCLC patients.

Expert opinion

Liquid biopsy should be considered not only as a valid alternative but as complementary to tissue-based molecular approaches. Careful attention should be paid to the optimization and standardization of all phases of liquid biopsy samples management in order to determine a significant improvement in either sensitivity or specificity, while significant reducing the number of ‘false negative’ or ‘false positive’ molecular results.

KEYWORDS:

• Liquid biopsy
• NSCLC
• ctDNA
• CTC
• biomarkers

Article highlights

• Although tumor tissue samples, histological or cytological, still arguably represent the gold standard starting material for the molecular assessment of clinical relevant biomarkers, a percentage of advanced-stage cancer patients, in particular non-small cell lung cancer (NSCLC) patients, do not have tissue availability to meet the requirements for adequate molecular testing purposes.

• In this setting, liquid biopsy plays a central role allowing molecular analysis and ensuring the best treatment options for advanced-stage cancer patients.

• Beyond blood, other body fluids or supernatants usually discarded after cytological preparations may be a valid source of nucleic acids for molecular analysis.

• Careful attention should be paid to pre-analytical (collection, centrifugation, extraction and storage), analytical, and post-analytical issues in liquid biopsy samples management.

• Liquid biopsy has demonstrated its complementarity with tissue-based analysis for different clinical purposes, including early diagnosis, predictive, and prognostic purposes and to monitor minimal residual disease and efficacy of target therapies in NSCLC patients.

Declaration of interest

Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, unrelated to the current work. Alfredo Addeo reports personal fees for attending advisory from Bristol‐Myers Squibb, AstraZeneca, Roche, Pfizer, Merck Sharp and Dohme, Astella, Eli Lilly and Boehringer‐Ingelheim. He has received fees for speaking bureau for Eli Lilly, AstraZeneca, MSD for work performed outside of the current study. Oscar Arrieta reports personal fees from Pfizer, grants and individual fees from Astra Zeneca, grants and individual fees from Boehringer-Ingelheim, Lilly, Merck, Bristol Myers Squibb, Roche, outside the submitted work. Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Foundation Medicine, Roche Diagnostics, Thermo Fisher, Broad Institute, BioNTech, Amgen, Flatiron Health, Teva Pharma, Rochem Biocare, Bayer, INQBox and The Foundation for Clinical and Applied Cancer Research – FICMAC. Additionally, he was linked and received honoraria as an advisor, participate in speakers’ bureau. He gave expert testimony to EISAI, Merck Serono, Jannsen Pharmaceutical, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly, Guardant Health, Illumina, and Foundation for Clinical and Applied Cancer Research – FICMAC; outside of the current study. Massimo Cristofanilli reports relation with Lilly, Pfizer, Menarini, CytoDyn, Archer Biosciences, AZ, G1 therapeutics, Sermonix, Olaris, Creatv Microtech. Foundation Medicine. He received research funding from Lilly, Menarini, Pfizer, Merck. Uncompensated relationship with Guardant Health, Predicine, Tempus, for work performed outside of the current study. Valeria Denninghoff has received personal fees (as a consultant and/or speaker bureau) from Thermo Fisher, BMS, Amgen, Novartis; MSD, and Roche; and their researches are sponsored by BMS, Novartis, Amgen, AstraZeneca, and Roche, unrelated to the current work. Ken O’Byrne reports: Consultant and/or Speaker Bureau BMS, Pfizer, Roche, AZ, Boehringer-Ingelheim, MSD, Pfizer, Merck, Novartis, Janssen, Yuhan, illumina, TriStar, Foundation Medicine. Shareholder and Director Carpe Vitae Pharmaceuticals; Shareholder Carp Pharmaceuticals and DGC Diagnostics; for work performed outside of the current study. Luis E. Raez gets research support from: Guardant Health, Exosomes DX, Liquid Genomics, BMS, Roche, Astra-Zeneca, Lilly Oncology, Loxo Oncology, Syndax, Merck, Pfizer, Genentech and Novartis, for work performed outside of the current study. Patrick Pauwels gets grants/research supports from AstraZeneca, Roche, Biocartis, MSD and receipts honoraria or consultation fees from AstraZeneca, Pfizer, Roche, MSD, BMS, Takeda, Biocartis, Novartis, Amgen, for work performed outside of the current study. Alessandro Russo reports consultancy/advisory board role for Astra Zeneca, MSD, and Novartis, for work performed outside of the current study. Maria José Serrano reports a patent for Isolation of Cells of Epithelial Origin Circulating In Peripheral Blood licensed to PCT/ES2018/070377. Giancarlo Troncone reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. Christian Rolfo is a speaker for Merck Sharp and Dohme (MSD), AstraZeneca, and Roche; research collaborations (non-financial support) with Guardant Health; advisory board activity for Archer, Inivata, Boston pharmaceutical, Novartis, and BMS and safety monitoring board for Md Serono. Research grant from LCRF-Pfizer; for work performed outside of the current study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.