Key result
Grade ≥3 cardiovascular toxicities occur in <10% of patients on amivantamab monotherapy, but exceed 20% when combined with lazertinib and chemotherapy, with thromboembolism being most common.
Why the study?
Amivantamab is used for locally advanced or metastatic NSCLC, but its cardiovascular toxicities are less examined.
What is the incidence of cardiovascular toxicities associated with amivantamab-based therapies in patients with NSCLC?
Systematic Review
What is the incidence of cardiovascular toxicities associated with amivantamab-based therapies in patients with NSCLC?
Amivantamab-based therapies for NSCLC are associated with significant cardiovascular toxicities, particularly thromboembolism, which are exacerbated when combined with lazertinib.
Higher CV toxicity with amivantamab combinations warrants monitoring in NSCLC; extends safety data for regimen selection in trials and practice.
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. • Amivantamab is a promising agent for EGFR-mutated NSCLC, with clinical studies indicating its efficacy and manageable toxicity • Clinical and real-world studies have shown an important incident of cardiovascular toxicities in patients treated with amivantamab-based therapies • Thromboembolism is the most common cardiovascular toxicity of amivantamab-based therapies • Combination of amivantamab with lazertinib increases the cardiovascular toxicity of amivantamab-based therapies
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Papassotiriou et al. (2025) conducted a systematic review in Locally advanced or metastatic NSCLC with EXON-20 mutation. Amivantamab was evaluated on Grade ≥3 cardiovascular toxicities. Grade ≥3 cardiovascular toxicities occur in <10% of patients on amivantamab monotherapy, but exceed 20% when combined with lazertinib and chemotherapy, with thromboembolism being most common.
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