Amivantamab-Chemotherapy Shows Longest Overall Survival in EGFR Exon 20 Insertion-Positive NSCLC

In a significant breakthrough for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions, the Phase III PAPILLON study has demonstrated that the combination of amivantamab and chemotherapy offers a longer overall survival compared to chemotherapy alone. The study, presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC), showed that patients receiving amivantamab-chemotherapy had a median overall survival of 34.3 months, compared to 27.9 months for those receiving chemotherapy.

The PAPILLON study, which enrolled 308 participants with previously untreated advanced NSCLC with EGFR exon 20 insertions, randomized participants to either the amivantamab-chemotherapy group or the chemotherapy group. The median follow-up period was 48.6 months. The overall survival results generally favored the amivantamab-chemotherapy group across predefined subgroups.

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The safety profile of the amivantamab-chemotherapy regimen was consistent with previous reports, and patient-reported outcomes also favored the treatment, with prolonged time to worsening across several key symptom scales. Importantly, among 128 participants in the chemotherapy arm who discontinued due to progressive disease, 97 (76%) received second-line amivantamab monotherapy.

The study's findings underscore the potential of amivantamab-chemotherapy as a foundational first-line regimen for patients with EGFR exon 20 insertion-positive advanced NSCLC. The adjusted analysis, which accounted for on-protocol crossover using the prespecified inverse probability of censoring weighting (IPCW) model, showed a significant survival benefit, with an adjusted hazard ratio of 0.57 (95% CI, 0.39-0.82; nominal P=0.003).

The International Association for the Study of Lung Cancer, which hosted the WCLC, is the largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from over 100 countries. The conference aims to increase awareness, collaboration, and understanding of lung cancer and help participants implement the latest developments globally.

The PAPILLON study's results represent a critical milestone in the treatment of EGFR exon 20 insertion-positive NSCLC, offering a promising new option for patients and potentially improving overall survival outcomes.