Amivantamab Plus Chemotherapy in Japanese Patients With <scp>EGFR</scp> Exon 20 Insertions <scp>NSCLC</scp>

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR Exon 20ins) are the third most common mutations in non-small cell lung cancer (NSCLC) and are associated with a poorer prognosis and resistance to conventional EGFR-tyrosine kinase inhibitors. This subpopulation analysis of the open-label phase 3 trial (PAPILLION) evaluates the efficacy and safety of amivantamab-chemotherapy versus chemotherapy among Japanese patients with locally advanced or metastatic NSCLC with EGFR Exon 20ins mutation (ClinicalTrials.gov, NCT04538664). Patients were randomized 1:1 to either intravenous amivantamab plus carboplatin/pemetrexed chemotherapy or chemotherapy alone. The primary endpoint was progression-free survival (PFS) by blinded independent central review; the secondary endpoints included objective response rate, duration of response, PFS after first subsequent therapy, overall survival, and safety. The overall population (n = 308) included 34 Japanese patients (amivantamab-chemotherapy, n = 19; chemotherapy, n = 15). Median PFS was 15.5 (95% CI 8.0, NE) months with amivantamab-chemotherapy compared with 5.6 (95% CI 3.0, 7.0) months (HR = 0.22 [0.09, 0.53]) for chemotherapy alone. Improvements in secondary endpoints were also greater in the amivantamab-chemotherapy arm than the chemotherapy arm. The predominant adverse events associated with amivantamab-chemotherapy were reversible hematologic and EGFR-related toxic effects; 2 of 19 patients discontinued all study agents due to treatment-emergent adverse events. Efficacy and safety results in this Japanese subpopulation were consistent with those in the overall population and support the first-line use of amivantamab-chemotherapy in this setting. Early identification of patients with EGFR Exon 20ins mutations, preferably with more sensitive next-generation sequencing-based methods, is important to ensure appropriate patient access to amivantamab-chemotherapy. Trial Registration: ClinicalTrials.gov, NCT04538664.