Preferred Treatment Options for EGFRMutated Exon 20 Insertion+ NSCLC

A recent Training Academy focused on the advancements of treatment for patients with non–small cell lung cancer (NSCLC). The panel focused on options for patients with EGFR mutations and exon 20 insertion. Here are their key takeaways in the space.

Biomarker Testing

• It is based on stage and histology and looks for PD-L1 expression.
  • The focus is on completing next-generation sequencing prior to treatment.
• Testing helps determine therapy options and which patients are the best candidates for neoadjuvant chemotherapy plus immunotherapy.

Treatment for EGFR-Mutated NSCLC

• Osimertinib (Tagrisso) monotherapy is considered the standard of care.
  • Treatment is based on results from the phase 3 FLAURA study (NCT02296125).¹
• Afatinib (Gilotrif) package insert is directed for uncommon mutations in NSCLC.²
• There are no head-to-head data for afatinib vs osimertinib.
  • Physicians should consider patients tolerance and central nervous system penetration for the treatment.

Treatment for Exon 20 Insertion+ NSCLC

• Amivantamab-vmjw (Rybrevant) plus chemotherapy was approved in March 2024 for patients with exon 20 insertion mutations.³
• Patients fit enough for chemotherapy should consider this combination because of the compelling efficacy results.
  • Patients with central nervous systemmetastases were excluded from the phase 3 PAPILLON trial (NCT04538664).

Unmet Needs in the Space

• Advancing risk-adaptive care
  • Focusing on risk stratification and personalized treatment
• Personalized therapy beyond the first-line setting
  • Performing new biopsies and identifying the mechanism of resistance
• Evaluating the minimum-tolerated dose vs the maximum-tolerated dose
  • Project Optimus was created by the FDA for this reason.⁴

References

1. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137
2. Gilotrif. Prescribing information. Boehringer Ingelheim; 2013. Accessed May 6, 2024. https://shorturl.at/kzEGW
3. FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. FDA. March 1, 2024. Accessed May 6, 2024. https://shorturl.at/GJKX9
4. Project Optimus. FDA. January 5, 2024. Accessed May 6, 2024. https://shorturl.at/dlsEF