EGFR L861Q

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

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

Post-transformation somatic mutation testing and germline testing at presentation revealed unique mutational profiles not previously reported in the setting of HT to SCLC. Further investigations are required to determine the optimal treatment and sequencing following HT.

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.

Significant associations were found between geographic origin, age, and sex with EGFR mutation status. This study confirms substantial genetic variability and geographical differences in EGFR mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Sep 2025 --> Dec 2026

P2, N=30, Active, not recruiting, Shanghai Chest Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2022 --> Dec 2027

Compared to other mutations, cells expressing EGFR L858M/L861R mutation were less sensitive to first-generation EGFR TKIs (gefitinib, erlotinib) and third-generation EGFR TKIs (osimertinib, lazertinib), whereas second-generation EGFR TKIs (afatinib, poziotinib) demonstrated potent inhibitory effects. The EGFR L858M/L861R mutation drives strong oncogenic signaling and exhibits preferential sensitivity to second-generation EGFR TKIs. These findings underscore the importance of accurate molecular diagnosis for guiding effective, personalized therapeutic strategies in NSCLC.