Prolonged complete metabolic response to chemotherapy combined with amivantamab with high grade cutaneous toxicity after osimertinib resistance in an uncommon T751_I759delinsAsp EGFR-mutant lung adenocarcinoma: a case report.

BACKGROUND

Amivantamab, an epidermal growth factor receptor-MNNG-HOS transforming gene (EGFR-MET) bispecific antibody with immune cell-directing activity, plus platinum-based polychemotherapy improved survival outcomes in patients with classical EGFR-mutant metastatic lung cancer previously treated by osimertinib. However, its efficacy in the context of uncommon EGFR alterations, particularly the Thr751_Ile759delinsAsp deletion in exon 19, which directly impacts the αC helix, remains uncertain.

CASE DESCRIPTION: This report presents a rare case of a young patient with metastatic lung adenocarcinoma (involving bone and lymph nodes) harboring an uncommon exon 19 deletion (Thr751_Ile759delinsAsp) in the EGFR gene identified with a Sanger sequencing after the negativity of a next generation sequencing (NGS). The patient demonstrated a one-year response to osimertinib. Following progression, he achieved a deep and prolonged response to amivantamab plus chemotherapy as second line, despite the absence of MET amplification. Amivantamab induced a high-grade cutaneous toxicity (erosive pustular dermatosis of the scalp) that led to its discontinuation with a sustaining complete response.

CONCLUSIONS

In non-smoker patients diagnosed with metastatic lung adenocarcinoma, comprehensive genetic profiling is essential to identify EGFR alterations and provide tailored treatment strategies. The detection of uncommon EGFR mutations requires the expertise and advanced technological platforms available in specialized centers. Data evaluating the efficacy of the news therapies mainly bispecific anti-EGFR/MET in patients with lung cancer harboring uncommon EGFR alterations are needed, as well as the relationship between toxicity and efficacy.