Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non–Small Cell Lung Cancer

Ray D Page,Leylah M Drusbosky,Hiba Dada,Victoria M Raymond,Davey B Daniel,Stephen G Divers,Karen L Reckamp,Miguel A Villalona-Calero,Daniel Dix,Justin I Odegaard,Richard B Lanman,Vassiliki A Papadimitrakopoulou,Natasha B Leighl

doi:10.1016/j.cllc.2021.10.001

Abstract

Background: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced nonsquamous non–small cell lung cancer (aNSCLC). The NILE study was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed nonsquamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed. Methods: This prospective, multicenter North American study enrolled patients with previously untreated nonsquamous aNSCLC who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis (Guardant360). 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. Results: Among 282 patients, 89 (31.6%) had an actionable biomarker, as defined by NCCN, detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) and 17 (52%) achieved a durable response > 6 months and 12 months, respectively. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (18 vs. 31 days, respectively; P = .0008). ConclusionscfDNA 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.

Highlights

First-line targeted therapies in advanced non-squamous non-small cell lung cancerhave demonstrated durable 50-90% objective response rates (ORR) [1,2,3,4].This exceeds outcomes with chemotherapy (29-49% ORR), immune checkpoint inhibitor monotherapy in patients with >1% progressive disease (PD)-L1 (ICI; 38-45% ORR), and even combination chemotherapy plus ICI in aNSCLC (40-65% ORR) [5,6,7]
In a large prospective, North American multicenter study conducted in mostly communitybased sites, the real-world impact of cfDNA genotyping on physician first-line treatment choice and patient outcomes is evaluated for the first time in previously untreated non-squamous aNSCLC
This study demonstrated a significant advantage for blood-based nextgeneration sequencing (NGS) to reduce the time to treatment initiation in the first line setting as compared to tissue-based profiling

Summary

Introduction

First-line targeted therapies in advanced non-squamous non-small cell lung cancer (aNSCLC)have demonstrated durable 50-90% objective response rates (ORR) [1,2,3,4].This exceeds outcomes with chemotherapy (29-49% ORR), immune checkpoint inhibitor monotherapy in patients with >1% PD-L1 (ICI; 38-45% ORR), and even combination chemotherapy plus ICI in aNSCLC (40-65% ORR) [5,6,7]. Various guidelines and expert consensus statements, including National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO) and International Association for the Study of Lung Cancer (IASLC), recommend plasma-based comprehensive genomic profiling (CGP) concurrently with tissue genotyping or when tissue is insufficient to test for all recommended genomic targets in patients with advanced nonsquamous NSCLC [8,10,11,12]. Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced non-squamous non-small cell lung cancer (aNSCLC). 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. Conclusions: 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.

Methods

Results

Conclusion