Comparison of liquid versus solid tissue genomic profiling for the prediction of chemo-immunotherapy benefit in advanced NSCLC

Background: Front-line genomic profiling in advanced NSCLC typically utilizes solid tissue, although assessment via liquid biopsy is becoming more frequent. In addition to detecting the presence of actionable mutations, genomic profiling can also be used to inform on the use of immune checkpoint inhibition (ICI), alone and in combination with chemotherapy (ICI+C). Using genomic profiling obtained from solid tissue (Foundation One CDx), we previously validated an algorithm capable of distinguishing advanced NSCLC patients with favorable ICI+C benefit from those with no benefit [1]. We have evaluated this algorithm in a cohort of advanced NSCLC patients receiving both liquid and solid tissue genomic profiling. Design: The ∆TRI algorithm uses Cellworks' computational model of a patient's tumor genomics to predict biomarker changes related to disease progression and potential benefit from ICI+C therapy. The previously validated ∆TRI and clinical threshold (∆TRI score of 16, which equates to a 15% increase in 24 month OS when receiving ICI+C) were evaluated in 20 non-squamous, advanced NSCLC patients with complete clinical and genomic information (Foundation One Solid and Liquid), derived from the nationwide (US-based) de-identified ConcertAI Genomics360 database. Differences in solid and liquid-derived ∆TRI scores were assessed for association with clinical factors as well as genomic markers. Results: Mutational profiles were highly similar between both platforms (median Jaccard index = 0.84), with 20% (4/20) of the patients having a Jaccard index < 0.5. In the 16 patients with differences between solid and liquid aberrations, discordance was driven 81% of the time by novel mutations identified in the liquid samples. Despite these differences, the ∆TRI scores generated from liquid biopsy samples were significantly correlated with those generated from solid tissue (R 2 = 0.61, p value < 0.001), with a median difference in ∆TRI score of 2.39, equating to roughly 2% difference in ICI+C benefit. Using the pre-defined clinical threshold of 16, 15% (n=3) of the samples switched from high ICI+C benefit category obtained from solid tissue (≥ 16 increase in 24 median OS with ICI+C) to a low/no benefit category ∆TRI score obtained with liquid samples, with an median difference in ∆TRI score of 7.4. Clinical factors such as the number of days between tissue and blood collection and number of metastatic sites were not associated with panel differences. Conclusions: Good similarity was observed in ∆TRI scores generated from liquid biopsy samples compared to scores generated from solid tissue, suggesting that with additional exploration liquid samples could be used for ∆TRI score generation. Discordant cases appeared to be driven by novel mutations identified via liquid biopsy. 1 Aggarawal et al, WCLC 2025