Abstract 6702: The clinical characteristics and outcomes of NSCLC patients with genomic alterations detected by blood-based NGS ctDNA assay
Authors: Wang Hsin-Yi , Ho Chao-Chi , Lin Yen-Ting , Liao Wei-Yu , Chen Chung-Yu , Shih Jin-Yuan , Yu Chong-Jen 
Published: April 2023

Background: The Blood First Assay Screening Trial (BFAST) (NCT03178552) is a prospective study screening for actionable genetic alterations using NGS of ctDNA among patients with treatment-naive advanced or metastatic NSCLC. We aimed to perform a more systematic investigation of genomic alterations in Asia/Taiwan NSCLC patients through the BFAST database at NTUH.

Materials and Methods: There was a total of 269 patients enrolled and receiving FoundationOne Liquid Companion Diagnostic (F1LCDx) assay at cancer diagnosis between Feb, 2019 and Mar, 2022 in NTUH. The concordance of tissue-based genetic testing in the real-life clinical setting and the blood-based NGS testing in the clinical trial were analyzed. The co-occurrence of genomic alterations detected with blood-based NGS ctDNA assay were also interpreted.

Results: A total of 206 patients (76.5%) detected driver mutations. Tissue-based genetic testing in the real-life clinical setting missed driver mutations in 67 (24.9%) patients with a sensitivity of 67.32%. Liquid NGS detected 38 (14%) patients with RET, KRAS, Met or ErbB2 mutations which were beyond the scope of current genetic testing in the clinical settings. Also, the F1LCDx assay detected more uncommon EGFR mutations than the Roche Cobas EGFR Mutation Test V2 (P &lt; 0.0001). Thirty-four (12.6%) patients had non-detected results in the F1LCDx assay which produced a sensitivity of 83.41%. By multivariate analysis, the predictors associated with discordant blood-based NGS ctDNA results were T stage (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.79, p = 0.012) and M stage (OR 0.21, 95% CI 0.09-0.49, p &lt; 0.0001). The most common co-occurring mutations in the blood-based NGS ctDNA assay were TP53, DNMT3A, TET2, PIK3CA and CTNNB1. Among the EGFR mutant population, first-generation compared to third-generation TKI use (hazard ratio [HR] = 0.43, 95% CI 0.22-0.85, P=0.02) and co-occurring genomic alterations in TET2 (HR = 2.35, 95% CI 1.15-3.48, P=0.02) were associated with shorter progression free survival of EGFR TKIs treatment in multivariate analysis. Disease stage was the only factor associated with overall survival in the EGFR mutant population.

Conclusion: NGS ctDNA analysis provided a more comprehensive genetic testing than conventional single gene testing kits. The lower stage which could imply lower or lack of ctDNA shedding into the blood was associated with a discordant result of the blood-based NGS ctDNA assay. Co-occurring mutations might have an impact on the treatment duration of EGFR-TKI.

Citation Format: Hsin-Yi Wang, Chao-Chi Ho, Yen-Ting Lin, Wei-Yu Liao, Chung-Yu Chen, Jin-Yuan Shih, Chong-Jen Yu. The clinical characteristics and outcomes of NSCLC patients with genomic alterations detected by blood-based NGS ctDNA assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6702.