Background: Non-small cell lung cancer (NSCLC) commonly presents at advanced stage. We previously reported systemic treatment uptake in stage IV NSCLC climbing from 55% (2009–2012) to 62% (2015–2017). Since then, first-line immunotherapy and 2nd/3rd generation tyrosine kinase inhibitors (TKIs) have emerged as standards of care. We explored whether treatment rates continued to rise and studied outcomes. Methods: We reviewed all cases of de novo stage IIIB/IIIC/IV NSCLC seen in out-patient medical oncology consultation at our institution between 2009–2012 (cohort A), 2015–2017 (cohort B), and June–December 2018 (cohort C). We compared rates of systemic treatment, molecular testing, targeted therapy, and immune checkpoint inhibitor (ICI) use. We compared survival in the overall, treated/untreated, younger and elderly population in cohort A vs. cohort B + C (=cohort D). Results: Cohorts A, B, and C included 528, 463, and 93 patients, respectively. Overall, 66% received any systemic therapy in cohort C, compared to 62% in cohort B and 55% in cohort A. Across three time periods, first-line chemotherapy rates fell (93, 76, 46%) while rates of first-line targeted therapy (5, 16, 15%) and ICI (0, 2, 36%) rose. Among molecular subtypes, first-line targeted treatment in EGFR-positive patients (63, 94, 100%) and anaplastic lymphoma kinase (ALK)-positive patients (0, 91, 100%) rose. Survival improved in all subgroups in cohort D vs. cohort A, except for patients ≥ 70 years and the untreated population. Conclusions: Systemic treatment rose across three time periods, reflecting the introduction of rapid diagnostic pathways, reflex molecular testing, ICI, and targeted therapies. Survival outcomes of advanced NSCLC patients have significantly improved.

Background: We performed a large-scale, retrospective, nationwide, cohort study of the incidence of brain metastasis in patients with advanced non-small-cell lung cancer (NSCLC) according to the systemic treatment administered. Method: The data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2011 to November 30, 2016. Of the 29,224 patients newly diagnosed with stage IIIB or IV NSCLC who received first-line cytotoxic chemotherapy (CC group) or targeted therapy (TT group), 22,508 patients without brain metastasis were analyzed. Result: In total, 1,131 (5.0%) patients subsequently developed brain metastasis. The overall cumulative incidence of brain metastasis was significantly higher in the TT group than in the CC group (1-year cumulative incidence: 8.7 ± 0.6% vs. 3.8 ± 0.3%; 3-year: 17.2 ± 0.7% vs. 5.0 ± 0.3%, respectively; P <0.001), despite the higher rate of brain metastasis in the CC group at <3 years after diagnosis. Younger age, female sex, living in a rural area, anticoagulant use, and first-line TT (relative risk, 2.17 ± 0.03; 95% confidence interval, 1.92e2.50, P <0.0001) retained significant associations with subsequent brain metastasis after adjusting for all variables. Conclusion: In the Korean population, the overall cumulative incidence of brain metastasis was significantly higher in patients in the TT group than in those in the CC group; the former could be regarded as having mutations in the EGFR or ALK gene.