Gilotrif (afatinib)

Cetuximab, a chimeric IgG1 monoclonal antibody anti-EGFR, is the only EGFR-targeted agent approved for HNSCC and has shown efficacy in both locally advanced (in platinum-unfit patients) and recurrent/metastatic (R/M) settings...Irreversible pan-HER tyrosine kinase inhibitors (e.g., afatinib, dacomitinib), dual-target bispecific antibodies such as duligotuzumab (EGFR/HER3), petosemtamab (EGFR/LGR5) or ficerafusp alfa (EGFR/TGF-β) have led to promising preclinical and early-phase clinical activity...While EGFR remains a valid therapeutic target, future efforts must focus on biomarker-driven patient selection and combination strategies to enhance efficacy and durability of response. Ongoing trials will further define the role of emerging anti-EGFR agents and their integration into HNSCC treatment algorithms.

Among older adults, 31 (97%) patients experienced AEs of all grades, and only six patients had grade ≥ 3 AEs with no grade 5 AEs. Afatinib demonstrated comparable therapeutic efficacy and safety in older and non-older adult patients with advanced EGFR-mutant NSCLC.Trial registration: UMIN-CTR identifier (UMIN000024935).

EGFR-TKI-resistant cell lines were established by long-term exposure to gefitinib, afatinib, and osimertinib via the PC9 model. Targeting endoplasmic reticulum (ER) stress pathways alongside immune checkpoint inhibitors may be crucial for overcoming resistance mechanisms identified here. These insights provide a rationale for personalized treatment strategies tailored to the immune-related gene-expression profiles observed in EGFR-TKI-resistant NSCLC models, aiming to enhance therapeutic responses and improve clinical outcomes.

This review provides a comprehensive overview of the evolution of four generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs): first-generation reversible inhibitors such as gefitinib and erlotinib; second- and third-generation irreversible inhibitors, including afatinib, dacomitinib, and osimertinib; and emerging fourth-generation agents, such as amivantamab. Future studies should explore combination therapies, antibody-drug conjugates, and next-generation allosteric inhibitors as promising strategies to overcome resistance. The evolution of EGFR-targeted therapy exemplifies the progress of precision oncology and serves as a basis for designing new paradigms in the management of lung cancer.

After multi-disciplinary treatment, the patient received concurrent chemoradiotherapy with pemetrexed and cisplatin, and achieved partial response. This patient did not receive durvalumab immunoconsolidation therapy for economic reasons...Patients with EGFR S768I/V769L compound mutated NSCLC may benefit from afatinib and osimertinib. Drugs with strong brain penetration capabilities are still needed for patients with S768I/V769L compound mutation to further improve survival outcomes.

MB49 cells were treated in vitro with lentiviral IFNα (LV-IFNα) gene therapy, with/without Afatinib, a pan-ErbB inhibitor, and cell viability and migration assays were performed...No mice in the combination therapy group died of drug toxicity. Our preliminary findings suggest that the ErbB pathway may serve as a clinically significant resistance mechanism to intravesical IFNα gene therapy, and when targeted concurrently, may improve treatment efficacy.

P2/3, N=174, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Nov 2025 --> Dec 2026

RAF1 is a key, non-redundant vulnerability in KRAS-driven lung adenocarcinoma. Co-targeting ARAF, EGFR, or DDR1 provides no additional therapeutic benefit in established disease. The absence of adverse effects from ARAF co-deletion suggests that RAF1 degraders with partial cross-activity towards ARAF are likely to be safe. These findings provide a strong preclinical rationale for developing RAF1-targeted degradation as a monotherapy for these malignancies.

Drug-gene mapping revealed candidates spanning already in clinical trials for HNC (e.g. Afatinib, Cabozantinib, Dasatinib, Brigatinib, Lenvatinib, Capivasertib, Erdafitinib) and emerging or repurposing candidates (Amuvatinib, XL765 (Voxtalisib), Golotimod, Artenimol, Quercetin, and Acetylsalicylic Acid), offering opportunities for precision repurposing...These included targeted therapies such as Fostamatinib, Nintedanib, Brigatinib, Regorafenib, and Lenvatinib, as well as emerging compounds like Artenimol, Quercetin, and Acetylsalicylic Acid (Aspirin). Through a combination of genomic analysis, network expansion, and literature validation, the GARD pipeline offers a powerful way to accelerate personalized cancer treatments while reducing cost and development time.

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..