Effectiveness of next-generation sequencing for patients with advanced non-small-cell lung cancer: a population-based registry study

Background: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. Materials and methods: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. Results: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). Conclusions: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.