The first-line standard therapy for locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients harbouring EGFR exon 20 insertions remains platinum-based chemotherapy, due to the lack of targeted therapies and no demonstrated benefit from immunotherapies. In this study, the addition of amivantamab, an EGFR mesenchymal–epithelial transition factor (MET) bispecific antibody, to chemotherapy resulted in superior efficacy outcomes for these patients, with a tolerable safety profile.
Alterations in the gene encoding epidermal growth factor receptor (EGFR) are among the most frequent activating mutations in non-small-cell lung cancer (NSCLC). Insertions in exon 20 are the third most common type of EGFR mutation, representing up to 12% of all EGFR-mutated NSCLCs. The first-line standard therapy for locally advanced or metastatic NSCLC with EGFR exon 20 insertions remains platinum-based chemotherapy, due to the lack of targeted therapies and no demonstrated benefit from immunotherapies. This study assessed the efficacy and safety of amivantamab, an EGFR mesenchymal-epithelial transition factor (MET) bispecific antibody, combined with chemotherapy, as first-line treatment in patients with advanced NSCLC harbouring EGFR exon 20 insertions.
The phase 3 PAPILLON trial enrolled patients with advanced NSCLC harbouring EGFR exon 20 insertions who had not received previous systemic therapy. In total, 308 patients were randomly assigned (1:1) to receive intravenous amivantamab plus chemotherapy (amivantamab–chemotherapy, n=153) or chemotherapy alone (n=55). The primary endpoint was progression-free survival (PFS). Patients in the chemotherapy group who had disease progression were allowed to cross over to receive amivantamab monotherapy.
After a median follow-up of 14.9 months, PFS was significantly longer in the amivantamab-chemotherapy group (11.4 vs. 6.7 months, respectively; HR[95%CI]: 0.40[0.30-0.53; p<0.001) compared to the chemotherapy group. At the 18-month mark, the PFS rate was reported at 31% vs. 3% in the amivantamab–chemotherapy and chemotherapy groups, respectively. A complete or partial response was observed in 73% vs. 47% of patients, respectively (rate ratio, 1.50; 95% CI: 1.32-1.68; p<0.001). In the interim overall survival analysis (33% maturity), a trend towards improved survival was observed with amivantamab–chemotherapy (HR[95%CI]: 0.67[0.42-1.09]; p=0.11). The most common adverse events (AEs) associated with amivantamab–chemotherapy were reversible haematologic and EGFR-related toxic effects, with 7% of patients discontinuing amivantamab due to adverse reactions.
The use of amivantamab–chemotherapy resulted in superior efficacy compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC harbouring EGFR exon 20 insertions.
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