"Lazertinib Proves Effective for Non-Small Cell Lung Cancer with Uncommon EGFR Mutations"

"Follow-up Studies Planned for Combination Therapies and More"

Clinical results have been released demonstrating the effectiveness of lazertinib in treating non-small cell lung cancer (NSCLC) with uncommon EGFR gene mutations.

On May 16, Professor Hong Minhee of the Yonsei Cancer Center's Lung Cancer Center and Professor Park Sehoon of the Department of Hematology and Oncology at Samsung Medical Center announced that the third-generation EGFR-targeted therapy lazertinib showed an objective response rate of 50% in patients with uncommon EGFR mutations. The results of this study were published in the journal of the International Association for the Study of Lung Cancer.

EGFR gene mutations are more frequently observed among Asians. While most cases involve exon 19 deletions or the L858R mutation, about 10?20% are classified as uncommon mutations such as G719X, L861Q, and S768I. These uncommon mutations tend to have lower response rates to standard therapies and fewer available treatment options compared to common mutations.

The research team conducted a clinical trial to evaluate the therapeutic effect of the third-generation EGFR-targeted therapy lazertinib in patients with uncommon EGFR mutations. This phase II multicenter study was conducted at five hospitals in Korea and included 36 patients with uncommon EGFR mutations who had not previously received treatment.

The objective response rate, defined as a tumor reduction of 30% or more, was 50%, and the disease control rate?which combines patients with tumor reduction and those whose tumors did not progress?was 88.9%. For mutations such as G719X, L861Q, and S768I, which account for 70?80% of uncommon cases, the response rate was 54.8%. Notably, among participants, patients with the G719X single mutation?the most common subtype?showed a response rate of 61% and a median progression-free survival of 20.3 months.

Adverse effects were not considered a significant concern. Although 33.3% of patients experienced grade 3 or higher adverse events as classified by the U.S. National Cancer Institute, these were manageable without dose reduction or discontinuation of the drug.

Additionally, the research team investigated resistance mechanisms to lazertinib by conducting blood tests before and after treatment. Some patients exhibited gene mutations not in EGFR but in APC, TP53, RET, ERBB2, and others, providing clues that could help guide subsequent treatment decisions.

Professor Hong Minhee stated, "This prospective study demonstrates that the third-generation EGFR-targeted therapy lazertinib can serve as a practical treatment option for patients with non-small cell lung cancer harboring uncommon EGFR mutations, for whom treatment options are limited. We are planning follow-up studies to explore ways to improve treatment outcomes, including combination therapies with other agents as well as monotherapy with lazertinib."