Amivantamab combined with carboplatin and pemetrexed is recommended by NCCN guidelines for NSCLC clinical practice as a first-line treatment for patients harboring EGFR exon 20 insertion

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Based on results from a phase 3, randomized PAPILLON trial presented at the 2023 ESMO Congress, amivantamab plus chemotherapy is recommended for treatment-naïve, locally advanced, or metastatic NSCLC patients diagnosed with EGFR exon 20 insertion (EGFR ex20ins) mutation. Amivantamab-Chemotherapy demonstrated significant clinical benefits over standard-of-care, and the latest NCCN guidelines recommend this regimen for frontline EGFR ex20ins.

Insertion in exon 20 of EGFR accounts for up to 12% of all EGFR-mutant NSCLC. Most subtypes of EGFR exon 20 insertions (EGFR ex20ins) are resistant to first to third-generation EGFR TKIs; hence, there is a significant unmet need for EGFR ex20ins treatment. Amivantamab is an EGFR-MET bispecific antibody with multiple mechanisms of action to present antitumor activity. Amivantamab has been approved for the treatment of patients with advanced NSCLC with EGFR ex20ins after platinum-based chemotherapy disease progression.

In the PAPILLON study, amivantamab combined with carboplatin and pemetrexed (Ami-Chemo) was compared with standard first-line platinum-based chemotherapy and was granted optional crossover to second-line amivantamab monotherapy after disease progression in the control arm. The primary endpoint of PAPILLON is progression-free survival by BICR according to RECIST v 1.1. At the data cut-off, the Ami-Chemo group met the primary endpoint, with a median progression-free survival (mPFS) of 11.4 months compared to 6.7 months in the control group (HR, 0.395; P<0.0001). Ami-Chemo reduced the risk of progression or death by 60%, and all the PFS subgroup analyses favored Ami-Chemo over the chemotherapy group. The objective response rate (ORR) also significantly increased in the Ami-Chemo arm, with 73% compared to 47% (OR, 3.0; P<0.0001). The remarkable finding was a significantly prolonged progression-free survival of subsequent therapy (PFS2) in the Ami-Chemo group over the control arm, with a median PFS2 not estimated (NE) in Ami-Chemo and 17.2 months in the control arm. Although interim overall survival was immature, a favorable trend was observed in the Ami-Chemo group. NCCN guidelines categorize amivantamab-chemotherapy as a new category 1 preferred first-line therapy in treatment-naïve patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion–mutated, nonsquamous NSCLC in 2024 version1. Ami-Chemo represents a new standard of care for frontline EGFR ex20ins.


  1. Nicolas Girard presented at 2023 ESMO, LBA5.
  2. Zhou et al., N Engl J Med. 2023 Nov 30;389(22):2039-2051.
  3. NCCN Guidelines NSCLC 2024 v1, NSCL-25