Dermatologic Adverse Event Mitigation and Management Strategies with Amivantamab + Lazertinib Therapy for Advanced Non-Small Cell Lung Cancer: A Vodcast

Targeted therapies have transformed outcomes of patients with advanced non-small cell lung cancer. Amivantamab, a bispecific antibody targeting epidermal growth factor receptor (EGFR) and MET, and lazertinib, a third-generation EGFR tyrosine kinase inhibitor, were approved in 2024 for the first-line treatment of EGFR-mutated (exon 19 deletion/exon 21 L858R substitution) locally advanced or metastatic non-small cell lung cancer. While EGFR-targeted therapies have demonstrated clinical efficacy, they are associated with on-target dermatologic adverse events (AEs). This vodcast aims to educate on strategies to mitigate and manage dermatologic AEs associated with amivantamab + lazertinib. The MARIPOSA study assessed amivantamab + lazertinib versus osimertinib in previously untreated patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. In the same population, the COCOON study assessed the impact of enhanced versus standard dermatologic management on the incidence of grade ≥ 2 dermatologic AEs. In MARIPOSA, amivantamab + lazertinib significantly improved overall survival (median not reached vs 36.7 months) and progression-free survival (median 23.7 vs 16.6 months) versus osimertinib. The most common EGFR-associated dermatologic AEs were rash and paronychia. To address these AEs, the COCOON study evaluated enhanced dermatologic management strategies (including prophylactic oral and topical antibiotics and moisturizer) versus standard of care dermatologic management, which resulted in a two-fold reduction in grade ≥ 2 dermatologic AEs with COCOON versus standard dermatologic management. We further discuss the COCOON prophylactic regimen together with reactive and expert-recommended dermatologic management approaches. In conclusion, amivantamab + lazertinib is an effective treatment that significantly improves overall survival. While dermatologic AEs are common, effective proactive management strategies, as demonstrated in the COCOON study, can help reduce the incidence and severity of dermatologic AEs. Prioritizing education for healthcare providers and patients will facilitate timely identification and proactive and reactive management of these events, ultimately improving the treatment experience for patients undergoing therapy with amivantamab and lazertinib.