Dermatologic prophylaxis and impact on patient-reported outcomes in first-line <i>EGFR</i> -mutant advanced NSCLC treated with amivantamab plus lazertinib: Results from the phase 2 COCOON trial.

Abstract

8641 Background: The phase 2 COCOONtrial (NCT06120140) is evaluating the impact of enhanced dermatologic management (DM) in combination with amivantamab (ami) + lazertinib (laz) on reduction of skin and nail adverse events (AEs). At the interim analysis, enhanced DM (COCOON DM) significantly reduced the incidence of grade ≥2 dermatologic AEs by Wk 12 vs standard of care dermatologic management (SoC DM). We assessed patient-reported outcomes (PROs) from COCOON to determine if reducing dermatologic AEs impacts the quality of life (QoL) of patients with EGFR -mutant advanced NSCLC. Methods: Participants (pts) with previously untreated EGFR -mutant (Ex19del/L858R) advanced NSCLC were randomized 1:1 to receive COCOON DM or SoC DM per site practice. Pts received the approved doses of IV ami + oral laz. COCOON DM included oral doxycycline/minocycline (100 mg BID Wks 1–12), clindamycin 1% lotion on scalp (QD Wks 13–52), chlorhexidine 4% to wash hands and feet QD, and non-comedogenic ceramide-based moisturizer to body and face QD. The COCOON DM arm received a digital health tool with training on dermatologic AEs and reminders to increase adherence to the DM regimen. Dermatologic symptoms and impact on pts’ health-related QoL were measured with PRO instruments every 2 weeks. The Skindex-16 questionnaire assesses the impact of skin conditions on QoL using 3 subscales (functioning, emotional, symptoms) and an average score (0 – no effect to 100 – effect experienced all the time). Patient’s Global Impression of Severity (PGI-S) is a self-reported 4-point rating scale (no symptoms, mild, moderate, severe) assessing severity of nail infection, skin condition, and rash over time. All P values reported are nominal. Results: As of 13 Nov 2024, 138 pts received COCOON DM (n=70) or SoC DM (n=68) and had ≥12 wks of follow-up (median, 4.2 mo). This analysis focuses on PROs through 12 wks of follow-up (three 28-day ami+laz treatment cycles). Substantial and consistent separation favoring COCOON DM was observed in all post-baseline Skindex subscales indicating lower severity of dermatologic AEs and reduced impact of those AEs on QoL. More specifically, at Cycle 3 Day 15 (~10 wks), a lower average Skindex total score was observed with COCOON DM vs SoC DM ( P =0.02). More pts in the COCOON DM arm vs SoC DM reported mild or no PGI-S rash, skin condition, or nail infection across the first 3 cycles. At Cycle 3 Day 15, there was a meaningful 3-fold difference for COCOON DM vs SoC DM in pts reporting no symptoms for PGI-S rash (21% vs 7%; P =0.04) and skin condition (23% vs 7%; P =0.02). There was also a numeric improvement in pts reporting no symptoms for nail infections (27% vs 16%; P =0.13). Conclusions: Among pts with EGFR -mutant advanced NSCLC, COCOON DM reduced the severity of dermatologic AEs and reduced the impact of those AEs on QoL compared to SoC DM. Clinical trial information: NCT06120140 .