Abstract B017: Clinical utility of next generation sequencing in advanced colorectal cancer: The earlier the better

Abstract

Background. Since next generation sequencing (NGS) was approved in solid tumor in Korea, it has been usually performed when patients were progressed on standard chemotherapy in advanced colorectal cancer (CRC).  Recently, new targeted agents have been developed rapidly, so the NGS is recommended as early as possible. In this study, we analyzed NGS results and investigated clinical benefit in advanced CRC.

Patient and method. Between October 2018 to December 2022, NGS data in 85 advanced CRC patients in St. Vincent’s Hospital, Suwon, Korea were retrospectively analyzed.

Results. Seven patients had metachronous, and others had synchronous metastasis. The median age was 58 (34-84), and 59 (69.4%) were male. Fourteen (16.5%) were right-side, 40 (47.1%) were left-side colon, and 30 (35.3%) were rectum. The median time from diagnosis of advanced CRC to NGS was 13 (0-81) months, and median time to death after NGS was 8 (0.3-43.0) months. NGS platform were ‘Oncomine comprehensive assay Plus’ in 71 (83.5%), and the others were various platforms in K-master project. NGS analyses revealed new therapeutic target in 17 (20%): high tumor mutational burden (n = 2), KRAS G12C (n = 4), KRAS (n = 1) or BRAF (n = 2) mutation not routinely screened at initial, BRAF class II mutation (n = 2), Her2/3 mutation (n = 2), and NTRK fusion (n = 1). Among those, two patients with KRAS G12C mutation enrolled in clinical trial of KRAS G12 inhibitor, and one patient with NTRK fusion received NTRK inhibitor (3.5% of total). Among RAS wild type population (n=30), we identified hyperselected patients (n = 18, [60%], absence of either KRAS, NRAS, PTEN, and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET or NTRK1 fusions by PARADIGM trial), which showed longer survival in cetuximab-treated population (p<0.001). Specific mutation including KRAS, NRAS, BRAF, TP53, or APC did not impact on prognosis. High TMB (≥10Mut/Mb) were associated with longer survival (p = 0.020). For patients with oligometastasis, hyperselected patients (p = 0.062) showed good prognosis.

Conclusion. The NGS results provided additional predictive or prognostic information in advanced CRC patients. Application of NGS as early as possible might help to make a clinical decision.

Citation Format: Ho Jung An, Hyunho Kim, Hyung Soon Park, Hyeon-Min Cho, Bong-Hyeon Kye, Ri Na Yoo, Ji-Yeon Moon, Sung Hwan Kim, Jonghoon Lee, Hyo Chun Lee. Clinical utility of next generation sequencing in advanced colorectal cancer: The earlier the better [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B017.