EGFR S768I

P3, N=744, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting

There is ongoing debate about the optimal choice of TKI for the rare EGFR mutations, but earlier reports indicate that these mutations may respond more favorably to second-generation TKIs compared to first-generation. This report underscores the significance of thorough molecular profiling in NSCLC.

The EGFR p.V774M/p.The S768I mutation contributed to improving the efficiency of furmonertinib-based therapy for NSCLC.

P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Jul 2025 --> Jul 2026

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

This study represents the largest cohort of NSCLC patients with EGFR G719X + S768I co-mutations treated with first-line afatinib. Our findings confirmed the effectiveness and safety of afatinib in this patient population. Furthermore, the presence of the G719X + S768I co-mutations serves as an independent predictor of favorable PFS for NSCLC patients. This study will provide new clinical evidence supporting afatinib therapy for patients with EGFR G719X + S768I co-mutations, both in China and globally. This study fills an important gap in the existing literature by providing robust, large-scale clinical data, offering new insights for the treatment of NSCLC patients with these uncommon mutations.

Furthermore, patients with EGFR-mutant lung adenocarcinoma undergoing treatment with EGFR tyrosine kinase inhibitors exhibited a significantly extended survival rate compared with those with wild-type EGFR receiving chemotherapy. In conclusion, the present study demonstrated that immunohistochemistry with pleural effusion cell blocks can aid in clarifying the histological subtype of lung cancer, and enable EGFR mutation detection, which can effectively guide molecular targeted therapy.

First-line osimertinib may provide real-world clinical benefits for patients with advanced NSCLC with atypical EGFR mutations, with results suggesting greater benefit in those harboring compound EGFR mutations.

P=N/A, N=20, Not yet recruiting, Cancer Hospital, Chinese academy of Medical Sciences; Cancer Hospital, Chinese Academy of Medical Sciences

P1/2, N=30, Not yet recruiting, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School; Nanjing Drum Tower Hospital, The Affiliated Hospital of Nan

The median duration of response was 16.1 months (95% CI: 10.3-NR) with a median follow-up time of 16.8 months.ConclusionAfatinib demonstrated encouraging efficacy in NSCLC patients with nonmajor uncommon EGFR mutations other than G719X, S768I, and L861Q, regardless of whether the mutations were solitary or compound. Comprehensive EGFR mutation profiling is crucial for identifying uncommon EGFR mutation patients likely to benefit significantly from afatinib.

The growth inhibitory effects of five novel 3G-TKIs, almonertinib, lazertinib, furmonertinib, rezivertinib, and befotertinib, in addition to currently available TKIs, were evaluated. In conclusion, afatinib exhibited broad activity and some 3G-TKIs showed promising efficacy in the front-line setting. Lazertinib is a potential second-line option after acquisition of resistance to afatinib or osimertinib.