Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial.
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Journal Volume
20
Journal Issue
10
Start Page
1517
End Page
1530
ISSN
1556-1380
Date Issued
2025-10
Author(s)
Cho, Byoung Chul
Li, Weimin
Spira, Alexander I
Sauder, Maxwell
Feldman, Jill
Bozorgmehr, Farastuk
Mak, Milena
Smith, Janellen
Voon, Pei Jye
Liu, Baogang
Tian, Panwen
Tan, Jiunn-Liang
Yang, Cheng-Ta
Karadurmus, Nuri
Cundom, Juan Esteban
Bertollo, Glaucio
Cicin, Irfan
Nieva, Jorge
Ortega-Granados, Ana Laura
Tomasini, Pascale
Nguyen, Danny
Felip, Enriqueta
Schuchard, Julia
Murphy, Sean P
Anderson, Bailey G
Romero, Tonatiuh
Xia, Yichuan
Sheng, Shubin
Bauml, Joshua M
Mahadevia, Parthiv J
Kam, Julian
Nematian-Samani, Mehregan
Simoes, Jairo
Wildgust, Mark
Girard, Nicolas
Abstract
Introduction: 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.
Subjects
Amivantamab
Dermatologic adverse events
Dermatologic management
Lazertinib
Non–small cell lung cancer
SDGs
Type
journal article