e20055 Background: Precision therapy improves outcomes in lung adenocarcinoma (LUAD) but requires accurate detection of actionable genomic alterations. Existing evidence demonstrates distinct genomic profiles between primary and metastatic LUAD. This real-world study systematically compared the landscape of actionable gene alterations between primary and metastatic lesions from Chinese LUAD patients. Methods: Chinese LUAD patients who had DNA-NGS testing were retrospectively enrolled. They were divided into the primary group and metastatic group based on sample source. The Chi-square test was performed to analyze differences in the prevalence of alterations (including mutations, amplifications, and fusions) in actionable genes ( EGFR, BRAF, KRAS, HER2, ALK, ROS1, RET, MET, NGR1, and NTRK ) between cohorts. Statistical significance was defined as p<0.05. Results: Two independent cohorts were established, with 3781 primary tumor samples and 424 metastatic tumor samples. The primary cohort had a mean age of 60.49 years (44.5% male; 55.5% female), and the metastatic cohort had a mean age of 62.4 years (55.2% male; 44.8% female). Mutations: EGFR and HER2 mutation rates were significantly lower in metastases ( EGFR : 50.94% vs 60.49%, p<0.001; HER2 : 3.54% vs 6.08%, p<0.05). No significant differences were observed for BRAF (4.7% vs 4.6%, p=0.89), KRAS (13.9% vs 11.0%, p=0.08), or MET (5.0% vs 3.9%, p=0.29). Amplifications: EGFR and MET amplification rates were significantly higher in metastases ( EGFR : 13.21% vs 6.06%, p<0.0001; MET : 5.42% vs 1.06%, p<0.001). HER2 amplification showed no significant difference (1.65% vs 1.16%, p=0.38). Fusions: ALK and ROS1 fusion rates were significantly higher in metastases ( ALK : 7.78% vs 5.32%, p<0.05; ROS1 : 3.77% vs 1.14%, p<0.0001). No significant differences were found for MET (0.2% vs 0.3%, p=0.91), NRG1 (0% vs 0.4%, p=0.18), FGFR (0.2% vs 0.5%, p=0.48), RET (2.6% vs 2.3%, p=0.65), or NTRK (0.2% vs 0.3%, p=0.91). Collectively, the overall rate of gene alterations analyzed above was significantly lower in metastases versus primary tumors (86.08% vs 89.55%, p<0.05). Conclusions: The landscape of actionable genomic alterations differs between metastatic and primary tumors in LUAD. This may be attributed to the intrinsic demographic factors (such as age and sex) within the two cohorts. Additionally, tumor evolution, clonal selection, and tumor heterogeneity may also partially explain these differences. The findings suggest that re-biopsy of metastatic lesions is crucial when patients experience disease progression, especially oligo-progression.
Liao et al. (Thu,) studied this question.