Enhanced Versus Standard Dermatologic Management With Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC: The COCOON Global Randomized Controlled Trial
Byoung Chul Cho, Weimin Li, Alexander I. Spira, Maxwell Sauder, Jill Feldman, Farastuk Bozorgmehr, Milena Perez Mak, Janellen Smith, Pei Jye Voon, Baogang Liu, Panwen Tian, Jiunn-Liang Tan, Cheng‐Ta Yang, Jin‐Yuan Shih, Nuri Karadurmuş, J. Cundom, Glaucio Bertollo, İrfan Çiçin, Jorgé Nieva, Ana Laura Ortega Granados, Pascale Tomasini, Danny Nguyen, Enriqueta Felip, Julia Schuchard, Seán Murphy, Bailey G. Anderson, Tonatiuh Romero, Yichuan Xia, Shubin Sheng, Joshua Bauml, Parthiv J. Mahadevia, Julian Kam, Mehregan Nematian‐Samani, Jairo Simoes, Mark Wildgust, Nicolas Girard
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.