Addition of Amivantamab to Chemotherapy in First-Line Treatment of Advanced NSCLC With EGFR Exon 20 Insertions

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The phase III PAPILLON study has shown that the addition of amivantamab-vmjw to chemotherapy significantly improved progression-free survival in the first-line treatment of advanced non–small cell lung cancer (NSCLC) with EGFR exon 20 insertions. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract LBA5) and reported in The New England Journal of Medicine by Caicun Zhou, MD, and colleagues.

Amivantamab, an EGFR/MET bispecific antibody, was granted accelerated approval in May 2021 for patients with advanced NSCLC and EGFR exon 20 insertions whose disease progressed on or after platinum-based chemotherapy on the basis of findings from the phase I CHRYSALIS study.

Caicun Zhou, MD

Caicun Zhou, MD

Study Details

In the international open-label trial, 308 patients who had not received prior systemic therapy were randomly assigned between December 2020 and November 2022 to receive amivantamab plus chemotherapy (n = 153) or chemotherapy alone (n = 155). Treatment consisted of amivantamab at 1,400 mg (1,750 mg for body weight ≥ 80 kg) given weekly for 4 weeks; the dose was then increased to 1,750 mg (2,100 mg for body weight ≥ 80 kg) given every 3 weeks until disease progression. Chemotherapy consisted of carboplatin at area under the curve = 5 for up to four cycles, and pemetrexed at 500 mg/m2 until disease progression. The primary endpoint was progression-free survival on blinded independent central review. Patients in the chemotherapy group with disease progression were permitted to cross over to receive amivantamab monotherapy.

Progression-Free Survival

Median follow-up was 14.9 months. Median progression-free survival was 11.4 months (95% confidence interval [CI] = 9.8–13.7 months) in the amivantamab group vs 6.7 months (95% CI = 5.6–7.3 months) in the control group (hazard ratio [HR] = 0.40, 95% CI = 0.30–0.53, P < .001). Rates at 6, 12, and 18 months were 77% vs 51%, 48% vs 13%, and 31% vs 3%, respectively.

Objective response was achieved in 73% of patients in the amivantamab group vs 47% of those in the control group (rate ratio = 1.50, 95% CI = 1.32–1.68, P < .001).

At interim analysis (33% maturity), median overall survival was not estimable in the amivantamab group vs 24.4 months (95% CI = 22.1 months to not estimable) in the control group (HR = 0.67, 95% CI = 0.42–1.09, P = .11). The numerically increased risk of death in the chemotherapy group was observed, despite the fact that 66% of patients in the group with disease progression crossed over to receive amivantamab monotherapy. Rates at 12, 18, and 24 months were 86% vs 82%, 74% vs 68%, and 72% vs 54%, respectively.


  • Amivantamab/chemotherapy significantly prolonged progression-free survival vs chemotherapy alone.
  • Median progression-free survival was 11.4 vs 6.7 months; rates at 18 months were 31% vs 3%.

Adverse Events

Grade ≥ 3 adverse events occurred in 75% of patients in the amivantamab/chemotherapy group vs 54% of the chemotherapy group; the most common in the amivantamab group were neutropenia (33%), leukopenia (11%), and rash (11%), and the most common in the control group were neutropenia (23%), anemia (12%), and thrombocytopenia (10%). Serious adverse events occurred in 37% vs 31% of patients. Adverse events led to discontinuation of any study drug in 24% vs 10% and to discontinuation of amivantamab in 11%. Adverse events led to death in seven patients (5%) vs four patients (3%), with one death considered related to amivantamab.     

The investigators concluded, “The use of amivantamab/chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions.”

Dr. Zhou, of Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Janssen Research and Development. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.