Nguyen Danny, Santos Edgardo S
Department of Medical Oncology and Therapeutics Research, City of Hope, Huntington Beach, CA, USA.
The Oncology Institute of Hope and Innovation, Broward County, FL, USA.
Target Oncol. 2025 Jun 21. doi: 10.1007/s11523-025-01163-3.
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.
靶向治疗已经改变了晚期非小细胞肺癌患者的治疗结果。阿米万他单抗是一种靶向表皮生长因子受体（EGFR）和MET的双特异性抗体，拉泽替尼是一种第三代EGFR酪氨酸激酶抑制剂，二者于2024年被批准用于一线治疗EGFR突变（外显子19缺失/外显子21 L858R替代）的局部晚期或转移性非小细胞肺癌。虽然EGFR靶向治疗已显示出临床疗效，但它们与靶向性皮肤不良事件（AE）相关。本视频旨在介绍减轻和管理与阿米万他单抗+拉泽替尼相关的皮肤AE的策略。MARIPOSA研究评估了阿米万他单抗+拉泽替尼与奥希替尼在既往未治疗的EGFR突变局部晚期或转移性非小细胞肺癌患者中的疗效。在同一人群中，COCOON研究评估了强化与标准皮肤管理对≥2级皮肤AE发生率的影响。在MARIPOSA研究中，与奥希替尼相比，阿米万他单抗+拉泽替尼显著改善了总生存期（中位生存期未达到 vs 36.7个月）和无进展生存期（中位生存期23.7个月 vs 16.6个月）。最常见的与EGFR相关的皮肤AE是皮疹和甲沟炎。为了解决这些AE，COCOON研究评估了强化皮肤管理策略（包括预防性口服和外用抗生素以及保湿剂）与标准皮肤护理管理的效果，结果显示与标准皮肤管理相比，COCOON研究使≥2级皮肤AE的发生率降低了两倍。我们将进一步讨论COCOON预防方案以及反应性和专家推荐的皮肤管理方法。总之，阿米万他单抗+拉泽替尼是一种有效的治疗方法，可显著提高总生存期。虽然皮肤AE很常见，但如COCOON研究所证明的，有效的积极管理策略有助于降低皮肤AE的发生率和严重程度。优先对医疗服务提供者和患者进行教育将有助于及时识别并积极主动地管理这些事件，最终改善接受阿米万他单抗和拉泽替尼治疗患者的治疗体验。
