Comprehensive management strategies for amivantamab-induced toxicities and review of the literature

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BackgroundLung cancer is a leading cause of cancer-related deaths, with Non-Small Cell Lung Cancer (NSCLC) comprising 85-90% of cases, most commonly adenocarcinoma. Key mutations include EGFR Exon 19 deletions and Exon 21 L858R. While third-generation TKIs like osimertinib, lazertinib, and aumolertinib are effective, resistance often arises. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-MET, shows promise, particularly against EGFR Exon 20 insertions.ObjectiveTo provide a comprehensive evaluation of the adverse effects associated with amivantamab in EGFR-mutant NSCLC, including their underlying pathophysiological mechanisms and evidence-based management strategies. In addition, this review aims to contextualize the clinical relevance of amivantamab by briefly outlining the therapeutic evolution of EGFR-targeted treatments, highlighting the rationale for its development, and current positioning in treatment paradigms.MethodsA comprehensive review of clinical trials, including CHRYSALIS, PAPILLON, MARIPOSA, and PALOMA-III, was conducted to assess the safety and efficacy of amivantamab. Practical and early insights into managing adverse effects of amivantamab are critical to better adherence and quality of life.ResultsAdverse effects were observed in most of the patients treated with amivantamab. Common side effects included cutaneous toxicities, diarrhea, infusion-related reactions (IRRs), vascular thrombosis and pneumonitis. The most frequent cutaneous side effects were rash, paronychia, pruritis, and stomatitis. Diarrhea occurred in patients primarily due to EGFR inhibition. IRRs were predominantly mild to moderate, occurring mainly during the first cycle. Thrombosis was a notable adverse effect observed, even in patients receiving anticoagulant prophylaxis. Pneumonitis was less common but severe.ManagementAdverse effects of amivantamab are managed based on severity. Cutaneous toxicities are treated with antibiotics, topical steroids, and dose adjustments. Diarrhea is managed with hydration, loperamide, and dose interruption. Infusion-related reactions (IRRs) are treated symptomatically, with epinephrine in severe cases. Anticoagulants are used for deep vein thrombosis or thromboembolism, and fibrinolytics or thrombectomy may be considered. Pneumonitis is managed by discontinuing amivantamab and using glucocorticoids.ConclusionsAmivantamab is effective for EGFR mutant NSCLC but can cause adverse effects. Understanding these effects and implementing management strategies can optimize outcomes, maintaining treatment efficacy.

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