Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control.

Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR T790M-positive non-small-cell lung cancer. We evaluated the effectiveness of lazertinib compared with osimertinib using an external control. We obtained individual patient data for the lazertinib arm from the LASER201 trial and the osimertinib arm from registry data at the Samsung Medical Center. In total, 75 and 110 patients were included in the lazertinib and osimertinib groups, respectively. After propensity score matching, each group had 60 patients and all baseline characteristics were balanced. The median follow-up duration was 22.0 and 29.6 months in the lazertinib and osimertinib group, respectively. The objective response rate (ORR) were 76.7% and 86.7% for lazertinib and osimertinib, respectively (p = 0.08). The median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI] 9.5-19.1) and 14.4 months (95% CI 11.8-18.1) for the lazertinib and osimertinib group, respectively (hazard ratio [HR] 0.97; 95% CI 0.64-1.45, p = 0.86). The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.

Epidemiology and Outcomes of Non-Small Cell Lung Cancer in South Korea.

Importance: Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. Objective: To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. Design, Setting, and Participants: This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. Main Outcomes and Measures: The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Results: Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. Conclusions and Relevance: This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.

Trends in Survival Rates of Non-Small Cell Lung Cancer With Use of Molecular Testing and Targeted Therapy in Korea, 2010-2020.

Importance: Over the past 10 years, treatment of non-small cell lung cancer (NSCLC) has been continually revolutionized. However, standard clinical trials may not reflect current multiple lines of treatment and corresponding outcomes in a timely manner. Objective: To investigate outcomes associated with new treatment of NSCLC in a clinical setting. Design, Setting, and Participants: This cohort study included patients with NSCLC between January 1, 2010, and November 30, 2020, who received any anticancer treatment at Samsung Medical Center in Korea. Data were analyzed from November 2021 through February 2022. Exposures: Clinical and pathological stage, histology, and major druggable sequence variation, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between 2 periods (period I: 2010-2015 vs period II: 2016-2020). Main Outcomes and Measures: The primary outcome was the 3-year survival rate of NSCLC. Secondary outcomes included median overall survival, progression-free survival, and recurrence-free survival. Results: Among 21 978 patients with NSCLC (median [range] age at diagnosis, 64.1 [57.0-71.0] years; 13 624 males [62.0%]), there were 10 110 patients in period I and 11 868 patients in period II; adenocarcinoma (AD) was the predominant histology (7112 patients [70.3%] in period I and 8813 patients [74.3%] in period II). There were 4224 never smokers [41.8%] in period I and 5292 never smokers [44.6%] in period II. Compared with patients in period I, patients during period II were more likely to undergo molecular tests in the AD (5678 patients [79.8%] vs 8631 patients [97.9%]) and non-AD (1612 of 2998 patients [53.8%] and 2719 of 3055 patients [89.0%]) groups. In patients with AD in period I, 3-year survival rates were 92.8% (95% CI, 91.8%-93.7%), 72.4% (95% CI, 68.3%-76.8%), 56.7% (95% CI, 53.4%-60.2%), and 28.7% (95% CI, 27.0%-30.4%) for stage I, II, III, and IV, respectively. In period II, 3-year survival rates of patients with AD were 95.1% (95% CI, 94.4%-95.9%), 82.5% (95% CI, 79.1%-86.1%), 65.1% (95% CI, 61.8%-68.6%), and 42.4% (95% CI, 40.3%-44.7%) for each stage, respectively. In patients without AD, 3-year survival rates were 72.0% (95% CI, 68.8%-75.3%), 60.0% (95% CI, 56.2%-64.1%), 38.9% (95% CI, 35.6%-42.5%), and 9.7% (95% CI, 7.9%-12.1%) for each stage in period I. In period II, the 3-year survival rates of patients without AD were 79.3% (95% CI, 76.3%-82.4%), 67.3% (95% CI, 62.8%-72.1%), 48.2% (95% CI, 44.5%-52.3%), and 18.1% (95% CI, 15.1%-21.6%) for each stage. Conclusions and Relevance: In this cohort study of 10 years of clinical data, survival outcomes were improved across all stages, with larger increases in patients with stage III to IV disease. The incidence of never-smokers and the use of molecular testing increased.