gefitinib

Patients were randomly assigned 1:1 to receive either rezivertinib (180 mg/d) plus gefitinib placebo or gefitinib (250 mg/d) plus rezivertinib placebo. The safety profile was consistent with previous analyses. Trial registration: NCT03866499 (ClinicalTrials.gov).

We report a 73-year-old woman with EGFR L858R-mutated NSCLC who developed LM after multiple lines of therapy, including gefitinib, osimertinib, chemotherapy, anti-angiogenic therapy, and radiotherapy. Treatment with high-dose furmonertinib (240 mg daily) combined with bevacizumab resulted in symptom relief and additional survival. Remarkably, her overall survival exceeded six years from initial diagnosis. This case highlights the potential role of dose-escalated furmonertinib as salvage therapy in LM after osimertinib resistance and underscores the importance of sequential and multimodal management in advanced EGFR-mutant NSCLC.

Pralsetinib was added to osimertinib, resulting in a response lasting 4 months...After one month with alectinib only, osimertinib was added due to the progression, resulting in another response of more than two months. Upon progression with quadruple alterations (EGFR 19del, EGFR C797S, MET amplification, and RET fusions), cabozantinib-gefitinib combination was initiated, leading to rapid deterioration...At the same time, comprehensive genomic testing remains essential for therapeutic decision-making, with ctDNA analysis complementing tissue-based approaches. Notably, the FGFR3-TACC3 fusion may represent a novel resistance mechanism contributing to the limited efficacy of EGFR-TKI.

A virtual cohort of 1,000 patients with advanced EGFR-mutant NSCLC received osimertinib (80 mg daily) or comparator first-line EGFR-tyrosine kinase inhibitors (gefitinib/erlotinib). Probabilistic analyses confirmed PMX superiority across willingness-to-pay thresholds. Pharmacometric models, enabling individualized dosing and exposure-driven effects, provide more biologically plausible estimates, supporting their integration into HTAs for precision oncology.

When combined with EGFR inhibitors (osimertinib and gefitinib) in PC9 cells, the mimics showed a higher rate of growth inhibition compared with the controls and reduced IC50 values. Similarly, conmiR-15/107 enhanced growth inhibition by the KRAS inhibitors sotorasib and adagrasib in H358 cells...Long-term assays showed that the mimics reduced the survival and delayed the proliferation of DTPs in osimertinib-treated PC9 cells as well as sotorasib-treated H358 cells. These findings support conmiR-15/107 as a potential adjunct to targeted therapy, capable of enhancing treatment efficacy and delaying resistance in lung adenocarcinoma.

Pharmacologic inhibition studies were conducted using the epidermal growth factor receptor (EGFR) inhibitor gefitinib to validate mechanistic links...These findings identify a previously unrecognized anti-tumor mechanism of KSM through inhibition of CHI3L1-EGFR-STAT3 signaling and suppression of M2-like TAM differentiation. KSM may therefore represent a promising immunomodulatory strategy for treating melanoma lung metastasis and other CHI3L1-driven malignancies.

Co-administration of YFSJ and gefitinib suppresses the growth and migration of NSCLC. ANKRD1 may be a potential biomarker for EGFR exon 20 mutation-driven resistance. This therapy reduces resistance to first-generation EGFR-TKIs by blocking YAP/ANKRD1 axis to suppress cell proliferation and promoting apoptosis. Based on our previous clinical investigations and the present preclinical findings, YFSJ-particularly in combination with gefitinib-may represent a novel therapeutic strategy and warrants further exploration for the treatment of NSCLC resistant to EGFR exon 20 mutations.

A focused translational approach that combines structural insights with innovative therapeutic strategies is urgently needed to achieve lasting clinical benefits in EGFR-driven cancers.

First-line treatment with the tyrosine kinase inhibitor afatinib was associated with improved OS compared with that of patients treated with erotinib or gefitinib. In addition, combination therapy with the angiogenesis inhibitor bevacizumab had a positive impact on OS...These findings highlight the importance of molecular profiling and individualized treatment strategies in optimizing OS for patients with advanced lung adenocarcinoma. Furthermore, the validated machine learning models may serve as useful tools for risk stratification and personalized prognostic assessment to support clinical decision-making.

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center

In vitro experiments using PC-9 cells included Cell Counting Kit-8 (CCK-8) assays (cell viability), wound healing assays (migration), flow cytometry (apoptosis/cell cycle), RNA sequencing (RNA-seq), public transcriptome datasets (GSE193258, GSE178975) were analyzed to compare ETS variant transcription factor 4 (ETV4) expression across EGFR-TKIs (aumolertinib, osimertinib, and gefitinib). ETV4 knockdown enhanced aumolertinib-induced apoptosis/G2/M arrest in vitro and synergistically suppressed tumor growth in vivo. These findings revealed that ETV4 enhanced the therapeutic efficacy of aumolertinib in vitro and in vivo, indicating that ETV4 is a potential therapeutic co-target, serving as a treatment strategy to prevent the acquired resistance induced by aumolertinib.

P1, N=94, Not yet recruiting, Fuzhou General Hospital