Amivantamab Plus Chemotherapy in Japanese Patients With EGFR Exon 20 Insertions NSCLC

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR Exon 20ins) are linked to poor prognosis in non-small cell lung cancer (NSCLC).
• These mutations confer resistance to standard EGFR-tyrosine kinase inhibitors, necessitating alternative treatment strategies.

Purpose of the Study:

• To evaluate the efficacy and safety of amivantamab-chemotherapy versus chemotherapy in Japanese patients with NSCLC and EGFR Exon 20ins.
• To assess amivantamab-chemotherapy's effectiveness as a first-line treatment for this specific NSCLC population.

Main Methods:

• A subpopulation analysis of the PAPILLION phase 3 trial (NCT04538664) involving 34 Japanese patients.
• Randomized 1:1 assignment to intravenous amivantamab plus carboplatin/pemetrexed chemotherapy or chemotherapy alone.
• Primary endpoint: progression-free survival (PFS) by blinded independent central review; secondary endpoints included objective response rate and overall survival.

Main Results:

• Median PFS was 15.5 months with amivantamab-chemotherapy versus 5.6 months with chemotherapy alone (HR=0.22).
• Amivantamab-chemotherapy showed improved secondary endpoints compared to chemotherapy.
• Adverse events were primarily reversible hematologic and EGFR-related toxicities; treatment discontinuation was infrequent.

Conclusions:

• Amivantamab-chemotherapy demonstrated superior efficacy and a manageable safety profile in Japanese NSCLC patients with EGFR Exon 20ins.
• Results are consistent with the overall trial population, supporting amivantamab-chemotherapy as a first-line option.
• Early identification of EGFR Exon 20ins mutations via sensitive methods is crucial for patient access to this therapy.