EGFR Exon 20 Insertion-Mutated Lung Cancer: Amivantamab and Chemotherapy Receive FDA Approval

On 1 March 2024, the Food and Drug Administration (FDA) in the United States approved, for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations, the following first-line treatment: amivantamab-vmjw (Rybrevant, Janssen Biotech, Inc.) with carboplatin and pemetrexed for use in combination.

At the same time, the FDA also converted a previously granted accelerated approval to traditional approval. In 2021, the FDA had granted accelerated approval to amivantamab for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease had progressed after platinum-based chemotherapy.

Amivantamab-vmjw is a bispecific antibody drug administered intravenously. Until now, approved drugs targeting EGFR mutations had been small-molecule medications in the TKI (tyrosine kinase inhibitor) class, taken orally as tablets.

New targeted treatments developed according to tumors' genetic characteristics are advancing the field of precision oncology day by day. Alongside new treatment options, we are also gaining a better understanding of lung cancer. This approval provides patients with EGFR exon 20 insertion-mutated non-small cell lung cancer with a targeted treatment option for the first time.

Lung cancer is the most common cancer worldwide and a leading cause of cancer-related death. Non-small cell lung cancer accounts for 80% to 85% of all lung cancers.

Approximately 2% to 3%of patients with non-small cell lung cancer have EGFR exon 20 insertion mutations, a group of mutations in a protein that causes rapid cell growth and consequently helps cancer spread. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

Turkey's Cancer Statistics report that 41264 people were diagnosed with lung cancer in Turkey in 2020. On this basis, EGFR exon 20 insertion mutations appear to account for lung cancer in approximately 1000 people each year.

The subtypes of lung cancer are shown below:

FDA Approval Based on the PAPILLON Trial

Effectiveness was evaluated in PAPILLON, a randomized, open-label, multicenter clinical trial involving 308 patients with EGFR exon 20 insertion mutations. Patients were randomly assigned 1:1 to receive amivantamab with carboplatin and pemetrexed or carboplatin and pemetrexed alone.

The primary efficacy endpoint, assessed by blinded independent central review, was progression-free survival (PFS), with overall survival as a secondary endpoint.

• Amivantamab plus carboplatin and pemetrexed significantly improved PFS compared with carboplatin and pemetrexed alone; the hazard ratio was 0.40 (95% CI: 0.30, 0.53; p-value<0.0001).
• Median PFS in the respective arms was 11.4 months (95% CI: 9.8, 13.7) and 6.7 months (95% CI: 5.6, 7.3), respectively.

Overall survival results were not yet mature at the current analysis.

The most common (20% or higher) adverse reactions were rash, nail toxicity, stomatitis, infusion-related reactions, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

The recommended amivantamab-vmjw dose is 1050 mg for patients with a baseline body weight <80 kg and 1400 mg for those weighing 80 kg or more, administered weekly for 4 weeks and then every 2 weeks until disease progression or unacceptable toxicity.