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

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.