Abstract A142: Risk of dermatologic adverse events with Amivantamab in EGFR-mutant non-small cell lung cancer: A meta-analysis of phase III trials

Abstract Background: Amivantamab is a bispecific antibody targeting EGFR and MET, approved for the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). As its use expands across various EGFR mutation subtypes and treatment lines, increasing attention has been given to its toxicity profile, particularly dermatologic adverse events (AEs). Early-phase trials and recent phase III studies have reported high rates of rash and dermatitis acneiform, including severe (grade ≥3) events. Given the potential impact of these toxicities on patient quality of life, treatment adherence, and clinical outcomes, a quantitative synthesis is warranted. This systematic review and meta-analysis were conducted to characterize the risk of dermatologic AEs associated with amivantamab in patients with EGFR-mutant NSCLC receiving treatment in phase III randomized controlled trials. Methods: A systematic literature search of MEDLINE and EMBASE was conducted from inception through July 10, 2024. Eligible studies included phase III randomized controlled trials (RCTs) evaluating amivantamab in patients with EGFR-mutant non-small cell lung cancer (NSCLC) that reported dermatologic adverse events (AEs). The pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated using the Mantel-Haenszel method. Statistical heterogeneity across studies was assessed using Cochran’s Q test. A random-effects model was applied to account for inter-study variability. Results: The analysis included 1,791 patients across three phase III randomized controlled trials: MARIPOSA (n=849), MARIPOSA-2 (n=636), and PAPILLON (n=306). The MARIPOSA and MARIPOSA-2 trials evaluated amivantamab-based regimens against standard therapies with 2:2:1 randomization, while PAPILLON compared amivantamab-chemotherapy to chemotherapy alone using a 1:1 ratio. Pooled results demonstrated a significantly higher incidence of dermatologic adverse events in the amivantamab-treated groups: any-grade rash occurred in 82.6% of patients receiving amivantamab versus 32.4% in the control group (RR 3.73; 95% CI: 1.37–10.13; p=0.010), and high-grade rash was reported in 15.2% versus 0.4% (RR 28.82; 95% CI: 10.68–77.76; p<0.00001). Similarly, any-grade dermatitis acneiform was observed in 26.6% of amivantamab-treated patients compared to 8.1% in controls (RR 5.24; 95% CI: 1.75–15.70; p=0.003), while high-grade dermatitis acneiform occurred in 6.5% versus 0% (RR 30.40; 95% CI: 5.98–154.62; p<0.0001). Conclusion: This meta-analysis demonstrates amivantamab is associated with a significantly increased risk of both any-grade and high-grade dermatologic adverse events, including rash and dermatitis acneiform, in patients with EGFR-mutant NSCLC. The elevated risk ratios highlight the need for heightened clinical vigilance and proactive dermatologic management strategies. Early identification and treatment of these toxicities are critical to maintaining patient quality of life, minimizing treatment interruptions, and ensuring sustained therapeutic benefit from amivantamab-based regimens. Citation Format: Jason Ta, Abbas Hussain, Riccesha Hattin, Daniel T. Jones, Ramaditya Srinivasmurthy, Rishi K. Nanda, Clinton Lam, Kyaw Z. Thein. Risk of dermatologic adverse events with Amivantamab in EGFR-mutant non-small cell lung cancer: A meta-analysis of phase III trials [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A142.