Liquid Biopsy Noninferior to Tissue-Based Genotyping in Management of Advanced NSCLC

Cell-free circulating tumor DNA (cfDNA)–based tumor genotyping is noninferior to tissue-based genotyping for detection of guideline-recommended biomarkers and therapeutic outcomes in patients with advanced nonsquamous non–small cell lung cancer (aNSCLC), according to study findings published in Clinical Lung Cancer.

In the treatment of aNSCLC, first-line therapies have demonstrated durable objective response rates that researchers note exceed outcomes with chemotherapy, immune checkpoint inhibitor (ICI) monotherapy in patients with less than 1% programmed death-ligand 1 (PD-L1) expression, and even combination chemotherapy plus ICI.

However, challenges have been cited in collecting adequate tissue biopsies to successfully perform comprehensive genomic profiling and identify National Comprehensive Cancer Network (NCCN)–recommended biomarkers, which help inform first-line therapy in patients with newly diagnosed advanced NSCLC.

“Undergenotyping of all 8 NCCN-guideline recommended genomic targets (mutations in EGFR, BRAF, MET, KRAS, rearrangements in ALK, ROS1, NTRK, RET) remains a major concern as a significant number of patients are not tested for all recommended biomarkers at diagnosis,” added the study authors.

With plasma-based genotyping having previously demonstrated in the NILE study to be noninferior to standard-of-care tissue biopsy in identifying targetable biomarkers among patients with NSCLC, researchers sought to further investigate clinical outcomes data of cfDNA-based tumor genotyping in this now matured patient cohort.

During the prospective, multicenter NILE study, participants with previously untreated nonsquamous aNSCLC had tissue genotyping and concurrent comprehensive cfDNA analysis performed (N = 282).

“Patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician’s choice of therapy had objective response rates, disease control rate, and time to treatment collected and compared to published outcomes,” they explained.

Of the study cohort, 89 (31.6%) had a NCCN-defined actionable biomarker detected by tissue (21.3%) and/or cfDNA (27.3%) analysis, and 61 (68.5%) of these patients were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1).

From those given targeted therapy, 33 patients were eligible for clinical response evaluation, with an objective response rate of 58% and a disease control rate of 94% identified. Moreover, 25 (76%) and 17 (52%) patients were shown to achieve a durable response of at least 6 months and at least 12 months or longer, respectively.

Notably, the time to treatment was significantly faster for cfDNA-informed biomarker detection, compared with tissue-based genotyping (18 vs 31 days; P = .0008).

“cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers,” concluded the study authors.

Reference

Page RD, Drusbosky LM, Dada H, et al. Clinical outcomes for plasma-based comprehensive genomic profiling versus standard-of-care tissue testing in advanced non–small cell lung cancer. Clin Lung Cancer. Published online October 10, 2021. doi:10.1016/j.cllc.2021.10.001