Gilotrif (afatinib)

P2, N=50, Completed, Yale University | Active, not recruiting --> Completed

P2, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Mar 2026 --> Sep 2026

The patient showed no meaningful response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including the first-generation (Icotinib), the second-generation (Afatinib) and the third-generation (Aumolertinib). Trophoblast cell surface antigen 2-antibody-drug conjugate (TROP2-ADC) and immune checkpoint inhibitors (ICIs) combined with Bevacizumab also resulted in limited efficacy. Based on the clinical features and treatment response of this case, we reviewed the published literature about the pathological characteristics, mutational landscape, and current therapeutic approaches for PEAC, with a particular focus on the therapeutic challenges and future research directions for EGFR-mutant PEAC, aiming to provide insights for clinical practice and further studies..

Afatinib 30 mg daily achieved comparable efficacy and better tolerability than 40 mg, with significantly longer PFS and OS in patients harboring compound or double-rare EGFR mutations. These findings suggest that lower-dose afatinib may optimize efficacy and safety in patients with uncommon EGFR-mutant NSCLC.

These findings suggest that DNMT1/3B-skewed methylation at the SOX9/DEFA5 promoters may be counteracted by ten-eleven translocation-mediated counter-demethylation. Collectively, our data indicate that afatinib modulates Paneth-like differentiation markers via DNA methylation-dependent repression of SOX9/DEFA5 and DNA methylation-independent induction of OSR1/RIP140 in Caco-2 cells, which may be relevant to crypt-associated epithelial function and gastrointestinal safety.

This study demonstrates that TMIGD2 is downregulated in BLCA and correlates with adverse prognosis and immune regulation. Its potential as a prognostic biomarker and therapeutic target is underscored by its involvement in key pathways, immune infiltration, and drug sensitivity. Further research is essential to fully realize the clinical potential of TMIGD2 in the management of BLCA.

Molecular docking revealed high-affinity binding between tepotiniband all six hub targets (Vina scores: -8.0 to -10.6 kcal/mol), providing a structural basis for the postulated mechanistic link to AKI. These findings not only highlight the necessity for enhanced renal monitoring in tepotinib-treated patients but, more broadly, establish the FAERS-NetDock Pipeline as a reusable, generalizable and hypothesis-generating framework for evaluating tyrosine kinase inhibitors (TKIs)-induced nephrotoxicity; this framework is immediately applicable to profiling the safety of other TKIs (e.g. crizotinib, capmatinib, savolitinib, afatinib and osimertinib) and is readily adaptable for de-risking a wider spectrum of targeted therapies.

Interestingly, these so-called NaJa lines displayed distinct differentiation states and responses to the clinically relevant RAF inhibitors (RAFi) encorafenib and exarafenib, thereby resembling the clinical heterogeneity of BRAFV600E-driven CRC. RAFi resistance was overcome by the EGFR-family inhibitor afatinib...Upon re-transplantation into syngeneic mice, all NaJa lines established aggressive tumors with distinct tumor microenvironments matching to their differentiation states. Thus, the NaJa lines provide a unique tool to study tumor heterogeneity, drug resistance and the interplay between tumor, stroma and immune cells in BRAFV600E-driven CRC.

Afatinib, a second-generation EGFR tyrosine kinase inhibitor, effectively suppresses primary tumor growth and extends progression-free survival in the patient with multifocal lung cancer and glioma driven by EGFR R252C. Our finding elucidates the activation mechanism of this extracellular EGFR mutation and demonstrates the efficacy of afatinib in treating lung cancer or glioma patients with this variant.

Finally, we propose a novel treatment strategy involving the synergistic inhibition of bladder cancer cell growth by combining TAK-901 with Afatinib. Our research strongly suggests that Aurora A and Aurora B are promising epigenetic therapeutic targets in bladder cancer. Furthermore, TAK-901 can function as a targeted kinase inhibitor and EGFR inhibitor for the treatment of bladder cancer by activating the FOXO signaling pathway, which induces apoptosis in bladder cancer cells.

After resolution with corticosteroids, treatment was switched to afatinib. This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.

Notably, co-targeting ERBB and AURK effectively overcame resistance in afatinib- and sotorasib-refractory models, wherein bypass activation of EGFR, ERK, and AURK was observed. Given the limited survival benefit associated with KRAS-targeted therapies and rapid emergence of resistance in clinical settings, our findings establish ERBB/AURK co-inhibition as a promising therapeutic strategy to improve durability of response and combat acquired resistance in KRAS driven LUAD.