Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: towards a proactive, multidisciplinary approach

Abstract

Contexte: The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed. Amivantamab is a bispecific anti-EGFR and anti-MET antibody with expected skin toxicities.

Objective: We developed here guidelines for prevention and treatment of cutaneous toxicities under amivantamab according to our experience at Institut Curie.

Materiel & method: The first patients with metastatic lung cancer harboring EGFR Exon20ins mutation, included in the phase 1 CHRYSALIS trial and cured at Institute Curie from November 1st 2019 until December 31st 2021 were selected for this work. Retrospectively, all cutaneous adverse events were registered and classified according to the CTCAE 6.0 classification, and actions we implemented to minimize and treat these adverse events were collected. We then developed guidelines based on these datas.

Results: A total of seven patients started amivantamab as monotherapy. The two most frequent dermatological adverse events were: acneiform rash and paronychia (100 % of patients). Other adverse events presented by the patients were reported: modification of hair growth with hypertrichosis in 50 % of men (n = 1/2) and hirsutism in 80 % of women (n = 4/5); skin abrasion of the scalp in 71 % (n = 5/7); and skin fissure in 57 % (n = 4/7). We recommend first a rigorous inspection of the skin and teguments to determine the risk rate to have dryer skin under treatment; second a prevention of paronychia/acneiform rash/and skin fissures with prophylactic tetracycline, skin moisturizing, and hygienic measures starting at least 14 days before treatment initiation; third a particular attention to the psychological impact of skin toxicities with access to psychological support.

Conclusion: We propose here guidelines for the management of dermatological toxicities under amivantamab with a multidisciplinary approach for the proactive management of cutaneous toxicities with a focus on preventive actions.

Keywords: Amivantamab; Dermatological toxicities; EGFR mutated; Guidelines; NSCLC.