Cho, Byoung ChulByoung ChulChoLi, WeiminWeiminLiSpira, Alexander IAlexander ISpiraSauder, MaxwellMaxwellSauderFeldman, JillJillFeldmanBozorgmehr, FarastukFarastukBozorgmehrMak, MilenaMilenaMakSmith, JanellenJanellenSmithVoon, Pei JyePei JyeVoonLiu, BaogangBaogangLiuTian, PanwenPanwenTianTan, Jiunn-LiangJiunn-LiangTanYang, Cheng-TaCheng-TaYangJIN-YUAN SHIHKaradurmus, NuriNuriKaradurmusCundom, Juan EstebanJuan EstebanCundomBertollo, GlaucioGlaucioBertolloCicin, IrfanIrfanCicinNieva, JorgeJorgeNievaOrtega-Granados, Ana LauraAna LauraOrtega-GranadosTomasini, PascalePascaleTomasiniNguyen, DannyDannyNguyenFelip, EnriquetaEnriquetaFelipSchuchard, JuliaJuliaSchuchardMurphy, Sean PSean PMurphyAnderson, Bailey GBailey GAndersonRomero, TonatiuhTonatiuhRomeroXia, YichuanYichuanXiaSheng, ShubinShubinShengBauml, Joshua MJoshua MBaumlMahadevia, Parthiv JParthiv JMahadeviaKam, JulianJulianKamNematian-Samani, MehreganMehreganNematian-SamaniSimoes, JairoJairoSimoesWildgust, MarkMarkWildgustGirard, NicolasNicolasGirard2025-11-022025-11-022025-10https://scholars.lib.ntu.edu.tw/handle/123456789/733351Introduction: Amivantamab plus lazertinib significantly improved progression-free and overall survival versus osimertinib in patients with previously untreated, EGFR-mutant advanced NSCLC. EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL). COCOON was conducted to assess prophylactic management and improve treatment experience. Methods: In the phase 2 COCOON study (NCT06120140), participants with previously untreated, EGFR-mutant, locally advanced or metastatic NSCLC received intravenous amivantamab plus oral lazertinib and were randomized 1:1 to enhanced dermatologic management (COCOON DM) or standard of care (SoC DM) per local guidelines. COCOON DM included oral doxycycline or minocycline (100 mg twice daily; weeks 1–12), clindamycin 1% (on scalp daily; weeks 13–52), chlorhexidine 4% (on fingernails and toenails daily), and ceramide-based moisturizer (on body and face at least daily). Primary end point was incidence of grade 2 or higher dermatologic AEs of interest (DAEIs) by week 12. Results: In total, 201 participants were randomized (99 to COCOON DM and 102 to SoC DM). At a median follow-up of 7.1 months, COCOON DM demonstrated significant reduction in the primary end point versus SoC DM (42% versus 75%; OR, 0.24; 95% confidence interval, 0.13–0.45; p < 0.0001). By week 12, the largest benefit with COCOON DM was observed in DAEIs involving the face and body (excludes paronychia; 26% versus 60%; p < 0.0001) and DAEIs involving the scalp (10% versus 26%; p = 0.0049). This benefit was maintained at 6 months, with significant reductions of DAEIs involving face, body, and scalp (excluding paronychia). Patient-reported outcomes favored COCOON DM, indicating reduced impact of dermatologic symptoms on QoL. Conclusion: An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidence of DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL.enAmivantamabDermatologic adverse eventsDermatologic managementLazertinibNon–small cell lung cancer[SDGs]SDG3journal article10.1016/j.jtho.2025.07.11740923969