Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial.

EGFR-targeted therapies are associated with dermatologic adverse events (AEs), which can affect quality of life (QoL).

EGFR 靶向治疗与皮肤不良事件（AEs）相关，可能影响生活质量（QoL）。

COCOON was conducted to assess prophylactic management and improve treatment experience.

COCOON 研究旨在评估预防性管理并改善治疗体验。

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.

在第二阶段的 COCOON 研究（NCT06120140）中，之前未经治疗、EGFR突变、局部晚期或转移性非小细胞肺癌（NSCLC）的参与者接受了静脉注射的阿米万坦单抗加口服拉泽替尼，并按1:1的比例随机分为增强皮肤管理组（COCOON DM）或标准护理组（SoC DM），按照当地指南进行。

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).

COCOON DM 包括口服多西环素或米诺环素（每日两次，每次100毫克；第1-12周），克林霉素1%（每日涂抹于头皮；第13-52周），氯己定4%（每日涂抹于手指甲和脚趾甲），以及基于神经酰胺的保湿剂（每日至少一次涂抹于身体和面部）。

Primary end point was incidenceof grade 2 or higher dermatologic AEs of interest (DAEIs) by week 12.

主要终点是第12周时2级或更高级别的皮肤相关不良事件（DAEIs）的发生率。

Results

In total, 201 participants were randomized (99 to COCOON DM and 102 to SoC DM).

共有201名参与者被随机分配（99人分配至COCOON DM组，102人分配至SoC DM组）。

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).

在中位随访7.1个月时，COCOON DM组与SoC DM组相比，在主要终点上显示出显著降低（42%对比75%；比值比，0.24；95%置信区间，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).

在第12周时，使用COCOON DM观察到的最大的益处是面部和身体（不包括甲沟炎；26%对比60%；p < 0.0001）以及头皮（10%对比26%；p = 0.0049）的DAEIs（皮肤不良事件）的改善。

This benefit was maintained at 6 months, with significant reductions of DAEIs involving face, body, and scalp (excluding paronychia).

这种益处在6个月时仍然保持，显著减少了涉及面部、身体和头皮（不包括甲沟炎）的DAEIs。

Patient-reported outcomes favored COCOON DM, indicating reduced impact of dermatologic symptoms on QoL.

患者报告的结果倾向于COCOON DM，表明皮肤症状对生活质量的影响减少。

Conclusions

An uncomplicated, widely available, prophylactic regimen (COCOON DM) reduced the incidenceof DAEIs with amivantamab-lazertinib and the impact of symptoms on QoL.

一种简单易得的预防性方案（COCOON DM）减少了与amivantamab-lazertinib相关的DAEIs发生率，并减轻了症状对生活质量的影响。