Gilotrif (afatinib)

The cytotoxicity of trametinib (MEK inhibitor), DT2216 (BCL-xL degrader) and afatinib (pan-EGFR inhibitor) and their combination was tested in patient-derived, primary PDAC cells using a live cell imaging system. Pathway analysis revealed the addition of afatinib in triplet regimen further inhibited PI3K/AKT effectors of p90RSK, p70S6K, and GSK3α/β along with a secondary pathway of P38 MAPK. Our study identifies an important contribution of EGFR inhibition to elevate the response of PDAC, supporting a clinical assessment of this triplet combination in patients.

In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.

We determined resistance profiles of 95% of all possible EGFR protein variants encoded in the whole tyrosine kinase domain against the common tyrosine kinase inhibitors afatinib, osimertinib and osimertinib in the presence of the co-occurring substitution T790M, in PC-9 cells. Our study has the potential to substantially improve the precision of therapeutic choices in clinical settings.

HER2 mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2 and EGFR mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.

Treatment of Ba/F3 or lung cells expressing MDK::ERBB2 with ERBB2 inhibitors (afatinib, poziotinib, tucatinib) blocked phosphorylation of ERBB2 and downstream effectors, and inhibited growth of both cell lines. ERBB2 fusions are rare oncogenic drivers that are candidates for targeted therapy. The subset of recurrent ERBB2 fusions with C-terminal/3' partners may represent an alternative mechanism of fusion oncogenicity.

P1/2, N=61, Recruiting, Jeeyun Lee | Not yet recruiting --> Recruiting

The YAP-HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment.

First-line treatment with Afatinib in elderly patients with NSCLC and EGFR mutations demonstrates significant efficacy and manageable toxicity in a Vietnamese multicenter real-life setting. The effectiveness of Afatinib was confirmed, with known and well-controlled adverse effects, supporting its use in this patient population.

Among agents targeting one or more members of the HER family, the pan‑HER family blocker afatinib was the most effective, inhibiting the proliferation of three out of seven human liver cancer cell lines (LCCLs), while the CDK inhibitor dinacicilib was the most effective agent, inhibiting the proliferation of all human LCCLs tested. Taken together, the present results suggested that EGFRvIII expression and its co‑expression with wtEGFR or CD44 was of prognostic significance. These results also support further investigations of the therapeutic potential of drugs targeting EGFRvIII and other members of the HER family in patients with HCC.

P1/2, N=25, Not yet recruiting, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

The TKIs used during this period include EGFR inhibitors such as afatinib, erlotinib, gefitinib, and osimertinib and ALK inhibitors such as alectinib and crizotinib. The EGFR-targeted and ALK-targeted therapies appear to have acceptable clinical response rate and safety profile in our population. Close and frequent monitoring of adverse events is advised to ensure a good quality of life and prevent serious complications.

P1, N=1200, Recruiting, Amgen | Trial completion date: Jun 2029 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Apr 2026

P2, N=102, Recruiting, Shanghai Jiao Tong University School of Medicine | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Jun 2025

In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib.

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Jun 2029 | Trial primary completion date: Sep 2025 --> Jan 2027

Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.

Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively...Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

In conclusion, MD simulations can effectively predict patient outcomes by connecting computational results with clinical data and advancing our understanding of EGFR mutations and their therapeutic responses.

P2, N=90, Active, not recruiting, Merus N.V. | Recruiting --> Active, not recruiting

Studies have shown that afatinib is beneficial for NSCLC patients with rare EGFR mutations...The results showed that WZ3146 induced cytotoxic effects, inhibited growth vitality and proliferation via ERK and AKT pathway in the EGFR G719X mutant cells. Our findings suggest that WZ3146 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation G719X.

For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin...Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance.

In this area, most of the recent hotspots are not focused on the basic research about paronychia due to the basic research about traditional paronychia already reached a relative mature stage. However, with the widespread clinical application of EGFRI anticancer drugs, the incidence of drug-induced paronychia is inevitably on the rise. Therefore, with the expanding diversity in the etiology of paronychia, this area deserves a multiple discipline cooperation with a much wider international communication.

Afatinib and pembrolizumab were found to have modest activity associated with irAEs after PD on previous EGFR TKI setting. Proinflammatory changes in immune cell subsets in tissue and blood were detected and associated with antitumor activity and irAEs.

P3, N=340, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Oct 2024 --> Apr 2025

Two patients died from infection following transplantation. Afatinib plus allo-HSCT may be an effective and safe new treatment strategy for RUNX1-RUNX1T1 positive AML patients with KIT-D816 mutation.

Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.

No abstract available

These derivatives were compared to the known tyrosine-kinase inhibitors in treating Chronic Myeloid Leukemia, i.e., imatinib and ponatinib. The addition of a methylpiperazine ring seems to be well distributed in the structure of afatinib when targeting the BCR-ABL enzyme, providing an important hydrogen bond interaction with the Asp381 residue of the DFG-switch of BCR-ABL active site residue and the AFA(IV) new chemical entities. Finally, in silico toxicity predictions show a favorable index, with some molecules presenting the loss of the irritant properties associated with afatinib in theoretical predictions.

After 2 months of afatinib treatment, significant tumor shrinkage was observed, and the patient's condition remained stable for 1 year. This case highlights the potential effectiveness of afatinib for treating rare stage IV lung adenocarcinoma with these specific EGFR mutations.

Blurry vision, caused by the choroidal metastasis, improved with first-line treatment with afatinib. Thereafter, osimertinib was administered as a second-line treatment, then chemotherapy containing pemetrexed plus bevacizumab as a third-line treatment...Only a few reports of lung cancer with choroidal metastasis provide long-term follow-up of more than five years. Therefore, the clinical course of this patient may provide some insights for long-term management in such cases.

Losartan exhibited dual effects on tongue squamous cell carcinoma cells. Moderate losartan concentrations facilitated cell proliferation, whereas high concentrations induced cytotoxicity in tongue carcinoma cells.

EGFR inhibition with afatinib or cetuximab in combination with RET TKIs was effective in addressing drug persistence. Consistently, knocking out EGFR or RET led to high sensitivity to RET or EGFR inhibitor respectively. Here, we have provided a comprehensive analysis of adaptive and acquired resistance against RET-rearranged NSCLC.

P=N/A, N=1, Completed, Pfizer | Recruiting --> Completed | N=20605 --> 1 | Trial completion date: Feb 2025 --> Jan 2024 | Trial primary completion date: Feb 2025 --> Jan 2024

Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.

The study of trends and characteristics suggested that OM is significantly more likely to occur in females and nonelderly patients and is likely to be induced by protein kinase inhibitors such as afatinib and everolimus. The results revealed that the agonist activity of the human pregnane X receptor, thyroid-stimulating hormone-releasing hormone receptor, and androgen receptor may be associated with OM development. Our study findings are expected to help avoid the risk of OM induction during the drug discovery process and clinical use of antineoplastic agents.

Exploration of the mechanisms behind their discriminative capabilities suggests that shared representations are strongly associated with gene functions, while mutation-specific and structure-specific representations are linked to mutagenic propensity and functional synergy, respectively. Finally, our in-depth analyses of these candidates suggest potential insights for individualized treatments: afatinib could counteract many mutation-driven risks, and targeting interactions with cancer gene SRC is a reasonable strategy to mitigate interaction-induced risks for NR3C1, RXRA, HNF4A, and SP1.

Despite maintaining a prolonged progression-free survival (PFS) with first-generation EGFR-TKI Afatinib, disease progression occurred in 2022 without detectable resistance mutations. Transition to second-generation TKI Furmonertinib resulted in poor control, with rapid progression including unusual bilateral breast metastases that exhibited inflammatory breast cancer-like peau d'orange changes...This case underscores the importance of continuous genetic profiling and tailored treatment approaches in managing advanced lung adenocarcinoma, particularly when presenting with rare metastatic sites and complex genetic landscapes. The successful application of Savolitinib following the identification of a MET amplification mutation highlights its potential in overcoming resistance mechanisms in NSCLC, providing a significant therapeutic option for similarly challenging cases.

This case highlights the importance of genetic profiling in patients with LSCC. Although these patients have a low positive rate of EGFR mutations, searching for EGFR mutations in these patients might broaden their treatment options.

Nontarget HER2 peptides provide normalization to the total protein. We show that HER2 occupancy by afatinib correlates directly to the inhibition of the receptor tyrosine kinase activity in NCI-N87 cells in culture and in vivo using those cells in a mouse tumor xenograft mode.

No abstract available

In a large real-world analysis, osi demonstrated superior progression-free and overall survival and improved tolerability compared to afatinib or erlotinib for atypical EGFR-mutated mNSCLC.

Finally, we conducted virtual screening against structurally similar compounds to afatinib and osimertinib and identified three compounds (CID 71496460, 73292362, and 73292545) that showed the potential to selectively inhibit EGFR despite the drug-resistance mutations. The WES-based study provides additional insight to understand the drug resistance mechanisms driven by tumor mutations and helps develop potential lead compounds to inhibit EGFR in the presence of drug resistance mutations.