Lazertinib 240mg tablets

Amivantamab, a newly introduced drug for locally advanced or metastatic NSCLC in patients with EXON-20 mutation, has shown promising results for prolonging progression-free survival and overall survival. Amivantamab's toxicities are common, especially those related to skin and infusion. However, its cardiovascular related toxicities are less examined. Therefore, the aim of this study was to perform a systematic review and concentrate available data for the cardiovascular toxicities of amivantamab in patients with NSCLC. This review was performed according to the PRISMA guidelines, and relevant studies were searched on three scientific databases, PubMed, Cochrane Library and ScienceDirect. In total, four phase-3 randomized clinical trials, three phase-1 clinical trials, and two real-world study were included in this systematic review. The results revealed that grade ≥ 3 cardiovascular toxicities are low in amivantamab monotherapy (<10 %), but their frequency increases when combined with lazertinib and overcome 20 % when amivantamab is combined with both lazertinib and chemotherapy. In addition, up to 3 % grade 5 cardiovascular events have been reported when amivantamab is combined with lazertinib. Pulmonary embolism and venous thromboembolism are the most common cardiovascular toxicities reported for amivantamab, and their risk increases when combined with lazertinib. These results indicate that amivantamab may be cardiotoxic, especially when combined with lazertininb, and cardioprotection should be considered in patients under amivantamab treatment.

Abstract licence: CC BY

BackgroundHead‑to‑head comparisons among first‑line third‑generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR‑mutated unresectable non-small cell lung cancer (NSCLC) are nearly absent. This network meta‑analysis compares the efficacy and safety of all available agents and provide evidence-based references for clinical decision-making.MethodsWe searched PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2026. Eligible studies were randomized controlled trials (RCTs) enrolling patients with advanced EGFR-mutated NSCLC receiving first-line third-generation EGFR-TKIs compared with first-generation EGFR-TKIs. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2 tool. The primary efficacy outcome was progression-free survival (PFS). We performed a network meta-analysis (NMA) using a fixed-effect model and ranked treatments using surface under the cumulative ranking curve (SUCRA). The protocol was registered with PROSPERO (CRD42022349097).ResultsEleven RCTs comprising 4,663 patients were analyzed. All investigated third-generation agents (aumolertinib, osimertinib, furmonertinib, befotertinib, limertinib, rilertinib, lazertinib, and rezivertinib) demonstrated superior PFS compared to first-generation TKIs. However, no statistically significant PFS differences were observed among the third-generation agents. Similarly, no significant differences were found between third- and first-generation TKIs regarding objective response rate (ORR) or ≥ G3 treatment-emergent adverse events (TEAEs). Subgroup analyses revealed no significant PFS benefit for befotertinib over first-generation TKIs in the L858R subgroup, nor for befotertinib or furmonertinib in elderly patients.ConclusionsMost third-generation TKIs offer superior PFS compared to first-generation agents, with comparable efficacy observed across the third-generation agents. Safety profiles, specifically regarding high-grade adverse events, appear similar between third- and first-generation TKIs.

Abstract licence: CC BY-NC-ND

First-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have transformed the management of advanced EGFR-mutated non-small cell lung cancer (NSCLC). Although randomized trials have demonstrated improvements in clinical outcomes, treatment decisions increasingly require consideration of health-related quality of life (HRQoL) and economic value. This systematic review synthesized evidence on HRQoL and cost-effectiveness of first-line EGFR-TKI therapies in advanced EGFR-mutated NSCLC. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement and prospectively registered in PROSPERO (CRD42024553180). PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from database inception to 31 March 2026. Eligible publications included randomized controlled trial reports assessing HRQoL using validated patient-reported outcome instruments and full trial-informed economic evaluations of first-line EGFR-TKI strategies. Risk of bias in HRQoL studies was assessed using the Cochrane Risk of Bias 2 tool, whereas the methodological quality of economic evaluations was assessed using the Drummond checklist. Owing to methodological heterogeneity, findings were synthesized narratively. A total of nine publications linked to six pivotal randomized controlled trials met the inclusion criteria, comprising four HRQoL reports and five trial-informed economic evaluations. Across the included studies, global health status and functional outcomes were generally maintained or improved from baseline, and no consistent clinically meaningful between-group differences were demonstrated; however, the limited evidence base does not establish equivalence between individual EGFR-TKIs. Economic findings varied across healthcare settings. Afatinib and aumolertinib were considered cost-effective within the settings examined, whereas osimertinib, dacomitinib, and lazertinib exceeded the willingness-to-pay thresholds used in the respective analyses. Cost-effectiveness was influenced by drug acquisition costs, model assumptions, analytical perspectives, and country-specific thresholds. Available randomized-trial evidence suggests that global HRQoL does not clearly differentiate the currently evaluated first-line EGFR-TKIs, as most treatments maintained overall health status and functioning despite differences in efficacy and toxicity. However, these findings should be interpreted cautiously given the limited number and heterogeneity of available HRQoL studies. In contrast, cost-effectiveness varied markedly across healthcare systems and appeared to be largely driven by drug acquisition costs and country-specific willingness-to-pay thresholds. The principal value distinction among first-line EGFR-TKIs may therefore lie less in global HRQoL and more in whether additional clinical benefit is considered affordable within the local healthcare setting.

Abstract licence: CC BY