Quantifying the Value of Multigene Testing in Resected Early Stage Lung Adenocarcinoma

Abstract

Introduction: Tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs), each requiring testing for precision biomarkers, have recently been approved in the adjuvant setting. We assessed the potential value of multigene testing in early lung adenocarcinoma (LUAD).

Methods: Using a real-world clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data, we selected patients with LUAD who underwent tissue comprehensive genomic profiling (CGP). Using a probabilistic decision tree, we estimated the cost implications of the avoidance of adjuvant ICI in patients with programmed death-ligand 1-positive (PD-L1+) LUAD and an ALK, ROS1 or RET driver.

Results: The CGP was performed on a specimen collected before advanced disease in 20% (1320 of 6697) of cases and ordered before advanced diagnosis for 12.6% (847 of 6697) of patients. The prevalence of driver alterations in early and advanced-stage specimens was similar, though KRAS mutations were enriched in early disease and drivers including ALK rearrangements in advanced disease. Patients who had CGP results obtained before versus after recurrence had less time between recurrence and the start of any first-line treatment (median 3.6 versus 6 wk, p < 0.001). Through avoidance of ICI in programmed death-ligand 1-positive early LUAD with an ALK, ROS1 or RET driver, we estimated that the universal CGP could reduce expected costs by $1597.23 per patient relative to EGFR single-gene testing.

Conclusions: The CGP can identify driver alterations and accelerate the start of first-line therapy at recurrence. It may also represent a cost-effective approach for avoiding futile adjuvant ICI in patients with drivers that have historically lacked activity with ICI in metastatic disease.

Keywords: Early disease; Genomic biomarkers; Lung cancer; Multigene testing.