AME case reports
Intracranial activity of amivantamab combined with carboplatin and pemetrexed in epidermal growth factor receptor exon 20 insertion-positive non-small cell lung cancer with brain metastases: a report of three cases
By Fujiwara Y, Tamiya Y, Yamaguchi T and 3 others.
Abstract
Background
Epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) mutations in non-small cell lung cancer (NSCLC) are largely insensitive to conventional EGFR tyrosine kinase inhibitors (TKIs) because of steric hindrance in the TKI-binding pocket. Amivantamab, an EGFR-MET bispecific antibody, has been approved for use in combination with chemotherapy as the first-line treatment for EGFR Ex20ins NSCLC. However, intracranial activity remains unknown because monoclonal antibodies are generally thought to have limited central nervous system (CNS) penetration.
Case description
We report three patients with advanced NSCLC with EGFR Ex20ins and with asymptomatic brain metastases who were treated with carboplatin, pemetrexed, and amivantamab (PAPILLON regimen). Case 1 was a 48-year-old woman with ≥10 asymptomatic brain metastases that developed during prior treatment with carboplatin, pemetrexed, and an investigational TKI targeting their EGFR ex20ins mutations; she achieved intracranial and extracranial partial responses. Case 2 was a 67-year-old man with postoperative recurrence and new brain metastases arising during another investigational EGFR-TKI monotherapy; he achieved a complete intracranial response. Case 3 was a 35-year-old man with previously untreated advanced lung adenocarcinoma and multiple asymptomatic brain metastases, which demonstrated intracranial and extracranial partial responses within two months.