LAUSR

Introduction: Various rare driver genomic variants have been investigated in metastatic non-squamous non-small cell lung cancer (mNSCLC). Individually they are considered rare (<3% prevalence), however, studies have shown collectively they represent up to 14.5% of the mNSCLC mutation profile. While multiple targeted therapies for rare variants such as NTRK fusions, MET exon14 skipping and RET fusions have been approved in the US for 1st line therapy in mNSCLC, other variants such as HER2 exon20ins, EGFR exon20ins, and FGFR-alterations are also gaining traction. This ever-growing number of actionable biomarkers is driving the need to use multi-gene testing such as NGS to ensure that actionable variants are tested prior to 1st line treatment. Here, we assessed US laboratory real-world NGS testing adoption and readiness that enables comprehensive genomic testing required to identify mNSCLC patients harboring any of these emerging actionable biomarkers. Methods: US NGS testing landscape in mNSCLC was assessed utilizing our Diagnostic Network for Precision Medicine (DXRX) data solution. Real-world data from 186,971 patients diagnosed with mNSCLC from Q12019 through Q32020 was used to calculate the NGS testing rate for these patients. NGS testing readiness and adoption for the top 25 US laboratories representing 70% of the overall US mNSCLC patient testing volume in 2019 was also assessed. Results: Overall, NGS testing rates in mNSCLC in the US dropped slightly from 58% in 2019, to an average of 53% in 2020 despite new targeted therapy approvals and changes in recommendations as described in ASCO/CAP and NCCN guidelines supporting NGS testing for mNSCLC patients. 84% of the top 25 labs offer in-house NGS testing for mNSCLC, accounting for 64% of the NSCLC testing volume. 55% offer NGS testing capable of identifying common and rare mutations such as HER2 ex20ins and EGFRex20ins. Additionally, 79% of these labs also offer RNA-based NGS panels, more suitable for detecting any fusions involving FGFR and NTRK genes. 24% of these NGS testing labs can test liquid biopsy samples, useful for tissue limited scenarios. Conclusion: Non-pharmaceutical interventions such as lockdowns to limit spread of COVID-19 infection are likely linked to the drop in testing rate observed in 2020 versus 2019. NGS is the desirable method that enables simultaneous, comprehensive testing to identify any actionable driver genomic variants present. However, adoption of NGS is still limited and highly centralized in the US. Today, only a small number of top labs can identify patients harboring any of this new wave of biomarkers for appropriate management. Barriers to NGS testing readiness and/or adoption include low demand due to lack of physician awareness and entrenched testing practices and conditions favoring sequential, single biomarker testing such as lab logistics, cost and reimbursement factors. Increasing awareness of clinical utility for broader genomic testing, which includes increasing involvement and effective use of tumor boards inclusive of pathologists to manage all mNSCLC patients will help establish the need and drive for use of NGS to ensure patients harboring common or rare actionable variants are identified. Keywords: Next Generation Sequencing, precision medicine, rare mutation