1422P - Comprehensive genomic profiling (CGP) changes management and improves survival in patients with advanced non-small cell lung cancer (aNSCLC)

Background

Advances in therapies for patients with NSCLC require personalizing treatment based on patients' tumor genetic profiles to improve outcomes. Approaches to evaluate tumor biomarkers include a range of testing from single gene/small panel to CGP which includes hundreds of genes and signatures like TMB and MSI. This study compared actionable biomarker detection, targeted therapy receipt, and clinical outcomes in patients with aNSCLC tested with CGP vs small panels (SP).

Methods

This is a retrospective study of adult patients in the US community setting diagnosed with aNSCLC between 1/1/2015 and 12/31/2020. Patients were followed from aNSCLC diagnosis (index) until the earliest of death or study-end and (9/30/2021) categorized based on the most comprehensive testing during follow-up as SP (≤52 genes) or CGP (>52 genes). Biomarker actionability was defined by OncoKB¹: FDA recognized (Level 1), standard of care (Level 2), standard of care predictive of resistance (Level R1). Likelihood of receipt of matched therapy was assessed using logistic regression; Kaplan-Meier and Cox proportional hazards models were used to assess real- world overall survival (rwOS).

Results

Among 3,884 patients (median age 68y, 50% female, 73% Non-Hispanic White), 20% received CGP and 80% SP as the most comprehensive test. The proportion of patients with ≥1 actionable biomarker was significantly higher in CGP than SP (32% vs 14%; p<0.001). Of patients with actionable biomarkers, 43%(CGP) and 38% (SP) received matched therapies (p=0.20). Among treated patients: (1) CGP prior to 1^st line treatment was associated with higher likelihood of receiving matched therapy (OR=3.21[95%CI: 1.98, 5.19]); (2) patients receiving CGP testing during follow-up had greater median rwOS (22 months[95%CI:18-25] vs. 15 months[95%CI:14-16]) and reduced risk of mortality (HR: 0.80[95% CI: 0.72, 0.89]) compared to SP.

Conclusions

Patients who received CGP had improved use of matched therapies and greater rwOS compared to SP. . Broader adoption of CGP may improve detection of actionable biomarkers, facilitating appropriate timely delivery of precision therapies resulting in better outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Syapse Inc.

Funding

Illumina, Inc.

Disclosure

G. Simon: Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, AstraZeneca, Dava Oncology, Merck, Reflexion, Genprex, Syapse , IDP Pharma, Onc. AI ; Financial Interests, Personal, Invited Speaker: Celegene, AstraZeneca, OncoLive, Nexus Oncology, PER Oncology; Financial Interests, Personal, Research Grant: Merck, BI. A. Berry: Financial Interests, Institutional, Stocks/Shares: Syapse; Financial Interests, Institutional, Full or part-time Employment: Syapse. B. Bapat: Financial Interests, Institutional, Stocks/Shares: Illumina. J. Law, C. Sweetnam, H. Mohammed, A. McBratney, M. Izano, M. Scannell Bryan: Financial Interests, Institutional, Full or part-time Employment: Syapse. S. Spencer, D. Hostin, B. Schroeder, P.G. Febbo: Financial Interests, Institutional, Full or part-time Employment: Illumina.