Updated IASLC Report Calls Liquid Biopsy Preferred Method of Molecular Testing

An updated consensus on liquid biopsy to detect non-small cell lung cancer (NSCLC) use has been published by the International Association for the Study of Lung Cancer (IASLC).¹

The statement argues that liquid biopsy is now a favored method of molecular testing in various clinical settings and that it has demonstrated that it is effective in conjunction with tumor tissue testing.² In addition, liquid biopsy offers unique opportunities such as serial monitoring and detection of minimal residual disease, according to the statement. Going forward, the IASLC expects a significant increase in the use of liquid biopsy.

The report discusses the inherent limitations of tumor tissue testing, which has traditionally been considered the gold standard for molecular analyses and argues that liquid biopsy approaches allow more varied methods of circulating analytes. According to the report, plasma circulating tumor DNA (ctDNA) represents the most widely studied and generally accepted alternative to tumor genotyping in solid tumors, including NSCLC.

“It is notable that the IASLC has taken the lead in detailing the current state of the art in this rapidly expanding field,” stated Gandara, MD, director of thoracic oncology, professor of medicine emeritus, in a news release. “Non-small cell lung cancer, in particular, is an ideal disease area for application of liquid biopsy due to the increasing availability of targeted therapies for this genomically complex malignancy. Liquid biopsy, and especially plasma ctDNA, can be used in many clinical settings where tissue is not applicable, such as the detection of minimal residual disease (MRD).”

The report builds upon a statement released by the IASLC in 2018 and was coauthored by a group of distinguished international lung cancer clinicians and experts.

In the report, the recommendations are as follows:

• In clinical practice, ctDNA collection, sample handling and automated processing should be performed using standardized and clinically validated procedures to reduce operator variability and false-negative results.
• Due to the growing number of guideline-recommended oncogene targets to be assessed in advanced NSCLC, testing of plasma ctDNA should be performed by a clinically-validated next-generation sequencing (NGS) platform rather than single gene PCR-based approaches, both in treatment-naïve patients and those associated with multiple mechanisms of acquired resistance to targeted agents. Where plasma NGS is not available due to technical and/or economic constraints, single gene or low multiplex-based approaches may represent appropriate alternatives. Use of limited PCR analysis for EGFR mutations as the initial step in molecular assessment, for example, remains highly relevant in areas of the world where the EGFR mutation rate is high. However, single gene testing should not be considered complete, and if negative, serial testing for additional actionable biomarkers must be pursued.
• The benefit of tissue and plasma NGS is now established in several clinical practice settings. It is anticipated, due to broad-based coverage of requisite oncogenes, decreased turn-around times and emerging data on cost effectiveness, that in the near future NGS will become increasingly available worldwide. Implementation of a multidisciplinary MTB to assist clinicians in treatment decision-making is advisable, as described above.
• Plasma ctDNA can now be considered a valid tool for genotyping of newly diagnosed patients with advanced NSCLC, and results are often complementary to tissue analysis. At the time of acquired resistance after tyrosine kinase inhibitor (TKI) therapy in an oncogene-driven NSCLC, initial use of ctDNA is preferred for determination of mechanisms of resistance ("plasma-first”), with repeat tissue biopsy if plasma ctDNA is uninformative. Due to ease of serial sampling and high patient acceptance, ctDNA is also emerging as the preferred method for real time monitoring.
• In patients with oncogene-addicted NSCLC, liquid biopsy is emerging as not only complementary to tissue-based analysis but also acceptable as the initial approach (“plasma first”) for biomarker evaluation at the time of diagnosis, as well as for monitoring the efficacy of targeted therapies. Finally, a plasma-first approach is appropriate for identification of mechanisms of acquired resistance to targeted therapies in many clinical settings.
• Indications for liquid biopsy in patients with non-oncogene addicted NSCLC are less well-defined at this time, although there are several promising areas of investigation. As noted above, tumor mutation burden is an emerging biomarker, pending completion of ongoing prospective randomized trials and refinement of methodology.

The 2021 World Conference on Lung Cancer, which will be held this upcoming September, will present a series of abstracts related to liquid biopsy methodologies and offer information regarding lung cancer screening, diagnoses, and therapeutic efficacy.

Reference

IASLC issues consensus updated report on liquid biopsies. IASLC. Press release. July 8, 2021.

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