Dermatologic adverse events associated with amivantamab: A multicentre study

Amivantamab is a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal–epithelial transition (MET), approved for the treatment of EGFR-mutant non–small cell lung cancer (NSCLC).1 Consistent with the toxicity profile of EGFR-directed therapies, amivantamab is associated with a high incidence of dermatologic adverse events (dAEs), which may affect treatment adherence.2, 3 However, real-world data describing the spectrum, severity and management of these toxicities remain limited. We conducted a retrospective, multicentre observational study across expert dermatology centres participating in the EADV Task Force ‘Dermatology for Cancer Patients’. All NSCLC patients who received at least one dose of amivantamab, either as monotherapy or in combination with lazertinib, chemotherapy or osimertinib, and developed at least one dAE were eligible. Demographic data, treatment regimens, dAE characteristics, management strategies and outcomes were collected. Comparative analyses were performed using chi-squared or Fisher's exact tests where appropriate. A total of 135 patients were included (Table 1). Overall, 16 distinct dAEs were identified; 65.9% of patients developed more than one toxicity and 26.7% experienced grade ≥3 events. The most frequent dAEs were acneiform rash (70.4%), paronychia (51.9%) and scalp ulcerative lesions (31.1%). Ulcerative lesions involving genital, perianal or oral mucosa occurred in 11.1% of patients (Figure 1). Compared with previously published smaller series, our cohort demonstrated a high frequency of scalp ulcerative lesions and severe dermatologic toxicities, likely reflecting referral bias inherent to specialized oncodermatology centres.3-5 Nevertheless, this real-world experience expands the currently recognized clinical spectrum of amivantamab-associated dAEs by documenting ulcerative lesions involving anatomical sites beyond the scalp, including genital, perianal and other cutaneous areas. Combination therapy with lazertinib was associated with a significantly higher number of dAEs compared with amivantamab monotherapy or amivantamab plus chemotherapy (p < 0.001). Paronychia occurred more frequently in the lazertinib group (p = 0.025), whereas genital and perianal ulcerations were more commonly observed among patients receiving chemotherapy (p = 0.010). Grade ≥3 toxicities were observed across all treatment groups, underscoring the need for dermatologic monitoring regardless of treatment regimen. From a treatment perspective, acneiform rash was mainly managed with oral tetracyclines, achieving high response rates. Escalation to low-dose isotretinoin or oral dapsone resulted in complete responses (CRs) in selected refractory cases. Among patients with paronychial lesions, 75.7% experienced concomitant acneiform rash and were treated with tetracyclines, with partial responses (PRs) observed in 77.3%. In selected cases, local interventions including nail phenolization or topical timolol were used with favourable outcomes (Table 1). Scalp ulcerative lesions represented one of the most challenging toxicities. Therapeutic approaches included oral tetracyclines, topical or systemic corticosteroids, topical antibiotics or combination regimens. The highest response rates were achieved with tetracyclines combined with topical or oral steroids, with 2 out of 13 patients (15.4%) achieving CR and 11 (84.6%) achieving PR. Cultures were obtained from scalp ulcerations from 16 out of the 42 patients, yielding positive results in 15 cases (93.7%). Antibiotic therapy guided by susceptibility testing led to CR or PR in most cases. Genital and perianal ulcerations were particularly difficult to manage, with systemic and/or topical corticosteroids resulting in only moderate improvement. Notably, these lesions were a leading cause of treatment interruption, occurring in most affected patients and often resolved rapidly following temporary discontinuation of amivantamab. Only six patients in our cohort received prophylactic dermatologic treatment with doxycycline (100 mg twice daily), developing only mild toxicities (grade 1 acneiform eruptions). Recent prospective data suggest that proactive dermatologic management may reduce the incidence and severity of selected dAEs, although certain toxicities, such as paronychia, remain difficult to prevent and treat.6 Taken together, these findings highlight the need for more targeted, evidence-based supportive care strategies as the clinical use of amivantamab continues to expand. In conclusion, amivantamab is associated with a broad and sometimes severe spectrum of dAEs in real-world practice. Awareness of characteristic ulcerative scalp and mucocutaneous presentations, together with timely dermatologic assessment, is essential to support continuation of oncologic therapy. No funding was received for this manuscript. There are no potential conflicts of interest associated with this particular manuscript. Ethics approval was given by the hospital ethics committee of each participating centre. The patients in this manuscript have given written informed consent to publication of their case details. The data that support the findings of this study are available from the corresponding author upon reasonable request.