First liquid biopsy for NSCLC to receive FDA approval

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Medical writer: Kirsty LEE | Last updated: 7th September 2020 | In: Breast Cancer, Gastrointestinal Cancer, Genitourinary Cancer, Gynaecological Cancer, Lung Cancer, Oncology, Targeted Therapies, US FDA Onc\Haem Approvals

Article Keywords

ALK, BRAF, cfDNA, CTC, EGFR, ERBB2, FISH, HER2, IHC, KRAS, MET, next-generation sequencing, NGS, non-squamous cell lung cancer, RET, ROS1, RT-PCR

The development of new targeted therapies for non-small cell lung cancer (NSCLC) in recent years has changed the standard of care for the later stages of NSCLC in specific population groups.¹ While initially these drugs failed in unselected patient populations, classification of tumour subtypes and identification of predictive biomarkers proved the concept of targeted molecular therapies in the clinical setting. Traditionally, tissue biopsies were required for genomic testing, but the quality, quantity and availability of tumour tissue pose challenges.²Besides, tracking the evolution of tumour cell genetic profiles over a patient’s treatment course with iterative tissue biopsies also presents a problem due to the invasive procedure.¹

More recently, the advent of next-generation sequencing (NGS) to determine alterations in the patient’s tumour molecular profile has led to novel use of this technology in liquid biopsies. A liquid biopsy tests for circulating tumour-specific markers, which include circulating tumour cells (CTC) or circulating free DNA (cfDNA), that are present in body fluids such as blood and urine.² It presents a less invasive option that can be easily repeated to provide a longitudinal assessment of the tumour genetic profile.² NGS can be applied to plasma CTC and cfDNA, and is thought to provide deeper insights on intra-tumour heterogeneity.²

The first diagnostic test to combine liquid biopsy and NGS, the Guardant360 CDx assay, was recently approved by the United States Food and Drug Administration (FDA), for use to identify tumours with specific mutations in the epidermal growth factor receptor (EGFR) gene in patients with metastatic NSCLC.³ It is approved to identify multiple solid tumour markers and also to identify EGFR mutations in patients who could benefit from treatment with osimertinib. It is currently not validated to test for other biomarkers.³

The Guardant360 CDx assay has a comprehensive NGS panel that identifies 7 guideline (G7) predictive biomarkers – EGFR, ALK, ROS1, BRAF, RET, MET, and ERBB2, and one prognostic marker, KRAS.⁴ It was previously investigated in the NILE study, for which the results were presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).⁴

In the NILE study, 282 patients with untreated non-squamous lung cancer undergoing standard-of-care tissue genotyping were prospectively enrolled and submitted a pre-treatment blood sample for cfDNA analysis using the Guardant360 CDx.⁴ A G7 biomarker was identified in the tissue of 21.3% patients, and 27.3% patients by cfDNA analysis (p<0.0001). The use of cfDNA increased the number of patients with an identified biomarker by 48%, including patients with negative, not assessed, or insufficient quantity tissue results.⁴ In patients without a G7 biomarker, 12.4% had an activating KRAS mutation, with 10.9% of which being identified by cfDNA.⁴ Median turnaround time for test results was significantly lower for cfDNA vs tissue genotyping (9 vs 15 days; p<0.0001).⁴

The approval of the Guardant360 CDx assay opens the potential for further adoption of genomic profiling in the field of oncology, with benefits of faster turnaround time and less invasive testing for patients.

Reference

Garinet S et al. J Clin Med. 2018;7(6).

Malone ER et al. Genome Med. 2020;12(1):8.

US Food and Drug Administration. FDA Approves First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test (Accessed 31 August 2020).

Leighl N. Abstract 4460 presented at the: AACR Annual Meeting 2019; April 2, 2019.

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).