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.

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.

CONCLUSIONS

These three cases provide clinical evidence that carboplatin, pemetrexed, and amivantamab may exert clinically meaningful intracranial antitumor activity in patients with EGFR Ex20ins NSCLC harboring small, asymptomatic brain metastases. Amivantamab, a bispecific antibody, combined with carboplatin and pemetrexed may exert clinically meaningful intracranial antitumor activity.