Liquid Biopsy Compared with Tissue Biopsy for Molecular Profiling in Patients with NSCLC

Conference Correspondent  - ASCO 2020 - Wrap Up

Obtaining sufficient tumor tissue for molecular profiling in patients with advanced lung cancer is a challenge. A prospective Canadian study is evaluating clinical outcomes and the utility of liquid biopsy for molecular diagnostic testing of patients with treatment-naïve stage IV lung adenocarcinoma as well as in the setting of resistance to targeted therapy. Results of the treatment-naïve cohort were presented at the 2020 ASCO Annual Meeting.

The VALUE study, a prospective study taking place at 6 Canadian centers, compares blood-based molecular profiling using the Guardant 360 (G360) assay with standard-of-care tissue-based profiling. The G360 assay is a validated cell-free DNA next-generation sequencing assay that identifies variants in 74 cancer-associated genes, including fusions and copy number gain. A cohort of 150 patients with treatment-naïve advanced nonsquamous lung carcinoma will receive liquid biopsy in addition to standard-of-care tumor tissue molecular profiling. Eligible patients have ≤10 pack-year smoking history and measurable disease. The primary end point is response to first-line therapy. Secondary end points include incremental targetable alterations amplified through the G360 assay, turnaround time of results, and successful molecular profiling rates.

To date, 84 eligible patients have been enrolled in the treatment-naïve cohort with a median age of 64 years (range, 23-91 years). Of the enrolled patients, 64% are female, 85% have never smoked, and 96% have adenocarcinoma. Actionable targets have been identified in 55% of patients using the G360 assay and in 39% of patients using standard tumor tissue biopsy. Eight EGFR/ALK aberrations were identified in tumor tissue biopsy but not in liquid biopsy, whereas 6 were identified in liquid biopsy but not in tumor tissue profiling. Tumor tissue profiling for EGFR/ALK was unsuccessful in 8% of patients due to insufficient tissue or failed biopsy. Fourteen (17%) patients had no cell-free tumor DNA alterations detected by G360 because of low disease burden or lack of shedding.

Of 75 patients in the cohort receiving first-line treatment, 57% received targeted therapy, 28% received chemotherapy combinations, 11% received checkpoint inhibitors, and 4% were observed. Treatment decisions were informed by G360 assay alone in 37% of patients and by the combination of G360 assay and tumor tissue biopsy results in 27%, based on physician report. Of 46 evaluable patients, the overall response rate (ORR) was 54%. With the use of the G360 assay, the ORR was 75% in patients with actionable alterations and 38.5% in those without. Using tumor tissue biopsy, the ORR was 67% in patients with actionable alterations and 44% in those without. The mean turnaround time for results was 7.9 days (standard deviation [SD] ± 1.7 days) for liquid biopsy and 19.9 days (SD ± 9.8 days) for tumor tissue biopsy.

The investigators conclude that in newly diagnosed lung cancer patients, liquid biopsy using the G360 assay identifies actionable targets beyond those identified by tumor tissue profiling alone. The turnaround time for liquid biopsy results is faster and outcomes are similar with both targeted and nontargeted therapy.

Source: 2020 ASCO Annual Meeting. Abstract 3546.

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Last modified: June 10, 2020