Clinical utility of comprehensive genomic profiling in non-squamous NSCLC with known actionable alterations
[Background]
Comprehensive genomic profiling (CGP) may provide additional therapeutic opportunities; however, its significance in patients with known actionable genomic alterations (AGAs) has not been established.
[Methods]
We retrospectively reviewed patients with non-squamous NSCLC who underwent CGP at the National Cancer Center Hospital between June 2019 and August 2025. Patients with known AGAs at CGP submission were included. CGP was mainly performed using NCC Oncopanel and FoundationOne CDx. The objective was to assess the frequency and impact of additional alterations and resistance mechanisms.
[Results]
Among 227 patients, 74 (32.6%) had known AGAs. Median age was 59 (29-82), 45.9% were male, and adenocarcinoma accounted for 90.5%. Targeted therapies had been administered before CGP in 60 patients (81.1%). AGAs included EGFR (n=54), KRAS (n=10), ALK (n=2), BRAF (n=2), RET (n=2), HER2 (n=2), ROS1 (n=1), and MET (n=1). CGP revealed additional actionable alterations in 24 patients, including EGFR (n=15) and others (n=9). Acquired resistance mutations were detected in 17, mainly EGFR (n=15), with one each in ALK (G1202R) and ROS1 (D2033N). Ten patients (13.5%) received new targeted therapies based on CGP. All had EGFR-positive tumors with pre-existing L858R (n=5) or exon 19 deletion (n=5). The alterations that guided therapy included RET fusions (n=4; CCDC6 [n=2], A
