Approaches to Uncommon EGFR Mutation
Dr. Cho Byoung Chul, Division of Medical Oncology Yonsei University College of Medicine, Republic of Korea

Epidermal growth factor receptor (EGFR) mutation is one of the key oncogenic mutations in non-small-cell lung cancer with adenocarcinoma histology. Exon 19 deletions and exon 21 L858R substitutions account for 90%, while EGFR exon 20 insertions constitute 4–10% of EGFR mutations and are the third most prevalent activating EGFR mutations.

Despite their introduction into clinical practice in the United States nearly 20 years ago, EGFR inhibitors began to truly transform patient outcomes only with the identification of EGFR activating mutations as biomarkers of response. Much less is known about uncommon EGFR mutations; however, with the increasing availability of NGS, they are more readily identifiable, and there is a growing body of information about the clinicopathologic characteristics and treatment response associated with these mutations.

EGFR exon 20 insertions are associated with decreased sensitivity to EGFR tyrosine kinase inhibitors and, until recently, effective targeted therapy against these tumours remained an unmet clinical need and chemotherapy was the only treatment of choice available.

The approval of amivantamab for patients who have progressed after chemotherapy represents an important step forward in the management of these patients.

Here in this session, we identify the common and uncommon driver mutations in NSCLC and describe the difference in patient outcomes associated with them, review the systemic treatments, including targeted therapies and ongoing clinical trials in EGFR exon 20 insertion mutations, as well as detection methods for EGFR exon 20 insertion. Lastly, resistant mechanisms and future directions are addressed.