Tagrisso (osimertinib)

Renal dysfunction occurred frequently during osimertinib treatment but was ameliorated after drug discontinuation, suggesting that, although renal function should be carefully monitored, its impairment is not likely to affect subsequent chemotherapy in most patients.

P=N/A, N=20, Not yet recruiting, Jilin Chemical Hospital; Jilin Chemical Hospital

P1, N=40, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

P3, N=630, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.

Known resistance mechanisms were observed on ctDNA analysis at progression. These observations demonstrate the benefit of osimertinib for treating EGFR-mutated PDAC and highlight the interest in investigating rare molecular alterations, especially in patients without KRAS alterations.

This multicenter cohort study demonstrated that stages I-III EGFR-mutated adenocarcinoma has a postoperative recurrence rate of 39.1%, and identified 7 independent risk factors for recurrence.

A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the IL-6 rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.

Furthermore, EGFR-mutated H1975dnMCAK cells, which frequently underwent chromosomal mis-segregation, demonstrated refractoriness to the EGFR-TKI osimertinib compared to control cells...Blockade of cGAS-STING-TBK1 signaling reversed EMT, resulting in restored susceptibility to EGFR-TKIs in vitro and in vivo. These results suggest that CIN may lead to the activation of cGAS-STING signaling in some EGFR-mutated NSCLC, resulting in EMT-associated EGFR-TKI resistance.

The discontinuation rate was significantly lower in patients who consulted a PLOC pharmacist than for those who did not (73% vs 97%, p = 0.008). However, the rates and reason for osimertinib discontinuation or dose reduction did not differ between groups.ConclusionPLOC consultation and intervention for the treatment of adverse events might have led to extending the duration of osimertinib treatment.

The combination of TKI/chemotherapy (osimertinib/carboplatine-pemetrexed) and TKI/bispecific antibodies (e.g., amivantamab/lazertinib) are alternatives under evaluation, with benefits in PFS but increased toxicity. Other emerging approaches include conjugated antibodies (patritumab deruxtecan, datopotamab deruxtecan) and next-generation TKIs. In the future, personalized treatment based on the molecular profile and early response to TKIs could optimize management, particularly by integrating predictive markers such as EGFR clearance under treatment.

No abstract available

No abstract available

This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors.

Additionally, immunofluorescence staining confirmed elevated expression of Ccl21 and Ccl8 in the distal bronchiolar epithelium. This study provides insights into the mechanisms underlying osimertinib-induced pneumonitis.

P2, N=5, Completed, Amsterdam UMC, location VUmc | Recruiting --> Completed | N=21 --> 5 | Trial completion date: Jan 2025 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024

This study confirms the real-world effectiveness of osimertinib in Peruvian patients with advanced EGFR T790M positive NSCLC and highlights the importance of timely detection and access to targeted therapies.

Furthermore, Piperlongumine significantly inhibited tumor growth in both Osimertinib-sensitive and resistant NSCLC xenograft models. These findings highlight the potential of Piperlongumine as an effective agent in overcoming EGFR-targeted therapy resistance and suggest new avenues for its clinical application in NSCLC treatment.

P2, N=60, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2028 --> Oct 2027 | Trial primary completion date: Apr 2028 --> Oct 2027

Recently, adjuvant osimertinib and alectinib therapy have demonstrated improved survival for patients with EGFR or ALK alterations, respectively, and they have been established as standard therapies. These studies highlight the necessity to assess EGFR and ALK status to guide treatment decisions for almost all NSCLC patients, regardless of whether they will undergo curative surgery, chemoradiotherapy, or as palliative chemotherapy. This review summarizes recent trials on perioperative and post-chemoradiation therapy and argues that molecular testing is required for non-metastatic NSCLC to improve patient outcomes.

For instance, targeted therapies are increasingly being integrated into early-stage management, with adjuvant osimertinib for EGFR-mutated NSCLC and alectinib for ALK-positive NSCLC demonstrating substantial survival benefits. Furthermore, emerging therapies such as bispecific antibodies, antibody-drug conjugates (ADCs), and novel immunotherapeutic agents show promise in addressing resistance mechanisms and improving outcomes in advanced-stage disease. Although new challenges arise, the evolving NSCLC treatment paradigm continues to prioritize precision medicine, offering hope for prolonged survival and enhanced quality of life for patients.

P2, N=400, Not yet recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd.

P1, N=336, Recruiting, Vivace Therapeutics, Inc | Phase classification: P1/2 --> P1 | N=250 --> 336

Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.

While third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, are commonly regarded as first-line therapies, recent studies indicate that crizotinib may offer superior disease control in certain EGFR-mutant patients, particularly those who exhibit poor responses to EGFR TKIs...In patients with EGFR/ROS1 co-mutation, gefitinib is generally effective as a first-line treatment; however, its efficacy can be limited, whereas crizotinib has demonstrated improved disease control. Future research should focus on identifying optimal treatment strategies for patients with EGFR/ROS1 co-mutation to enhance patient outcomes. In conclusion, this case report not only illustrates the effectiveness of crizotinib in managing patients with EGFR/ROS1 co-mutation but also underscores the importance of personalized treatment approaches, offering valuable insights for improving clinical outcomes in NSCLC patients with complex genetic profiles.

Additionally, we discovered that piperlongumine could enhance the interaction between E3 ligase RNF4 and Sp1, inhibit the phosphorylation of Sp1 at Thr739, facilitate the ubiquitination and degradation of Sp1, lead to c-Met destabilization, and trigger intrinsic apoptosis in resistant cells. In summary, our study sheds light on the potential of piperlongumine in overcoming osimertinib resistance, offering new strategies and perspectives for the clinical management of drug-resistant NSCLC.

In the FLAURA trial, osimertinib demonstrated longer progression-free survival (PFS) and overall survival (OS) compared to gefitinib or erlotinib. However, the clinical impact of dose reduction is not fully understood. Physicians should carefully weigh its benefits and risks before implementation.

The combination of the two drugs is markedly more effective than the use of drugs alone. In conclusion, the study demonstrated that Rapamycin combined with Osimertinib can inhibit the cell migration, regulate the cell cycle, promote the autophagy and apoptosis, increase the ROS level and regulate the PARP, MAPK/EKR, and Akt/mTOR pathways in A549 and PC-9 cells, providing a novel theoretical basis for their clinical treatment of NSCLC.

Our analysis suggests that exclusionary EGFR testing is a cost-effective strategy for Taiwanese patients newly diagnosed with advanced lung adenocarcinoma.

The tumor receded, but eventually irreversible thrombocytopenia developed. For patients with severe lung cancer, anti-tumor efficacy and adverse events should be closely observed during anti-tumor therapy.

Furthermore, further characterization of these resistance mutations beyond somatic mutations can aid in development of future therapeutic options, which currently do not exist. It is recommended that germline testing be performed as part of the initial patient workup, if available.

Next generation sequencing (NGS) identified an EGFR Ex19del mutation, which suggested the use of afatinib, as it was prescribed prior to osimertinib and was covered by insurance...Moreover, ALK and ROS1 were identified through immunohistochemistry (IHC), with ROS1 expression subsequently confirmed by fluorescence in situ hybridization (FISH); this prompted a switch to crizotinib, which was discontinued owing to further disease progression...A subsequent biopsy indicated a transformation to large cell neuroendocrine carcinoma, which led to treatment with platinum-etoposide chemotherapy and, later, paclitaxel and osimertinib, both of which are partially effective. Finally, a new biopsy confirmed ALK positivity in a large cell neuroendocrine carcinoma that was still harbouring an EGFR exon 19 deletion, so alectinib was introduced...These findings underscore the necessity of monitoring patients with oncogenic addiction through both liquid biopsy for on-target mechanism detection and tissue sampling to detect histological transformations. These mechanisms can occasionally be combined, thereby providing comprehensive panels at each stage of tumour progression.

P=N/A, N=100, Recruiting, Guangzhou Medical University | Trial completion date: Mar 2026 --> Sep 2026 | Trial primary completion date: Mar 2025 --> Jun 2026

P1, N=81, Active, not recruiting, AbbVie | Trial primary completion date: Feb 2025 --> Aug 2025 | Trial completion date: Feb 2025 --> Aug 2025

No abstract available

MRD detection could potentially identify patients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmation. ClinicalTrials.gov identifier: NCT02511106 .

In addition, compound 5 showed low cytotoxicity in Vero cells with an IC50 value of 2.84 ± 0.13 μM which is two-fold less cytotoxic than osimertinib...Molecular dynamics simulation confirmed the strong interaction between compound 5 and TACE, a crucial element in the EGFR and IL-6 signaling pathway's reduction which may lead to a decline in the survival rate of colon cancer. These findings indicate compound 5 as a promising anti-colon cancer drug candidate.

Keyword co-occurrence analysis revealed significant research topics including "gefitinib", "chemotherapy", "open label", and "erlotinib." Moreover, keyword burst analysis indicated notable periods of increased research focus on topics such as "osimertinib" and "liquid biopsy", suggesting emerging trends and current hotspots in the treatment of EGFR-mutated NSCLC. This analysis highlights research trends on TKIs for EGFR-mutated NSCLC, emphasizing the importance of targeted therapies like gefitinib and osimertinib for future research and clinical practice enhancement.

After several subsequent lines of treatment including erlotinib and carboplatin+pemetrexed+osimertinib, repeat genetic sequencing identified a HER2 exon 20 insertion (A775_G776insYVMA) in both blood and tissue. This report represents the first published case detailing the safety and efficacy of a combination fam-trastuzumab-deruxtecan and osimertinib in a patient with NSCLC and HER2-mutated resistance after EGFR-targeted therapy. The findings from this report suggest that fam-trastuzumab-deruxtecan can be safely given in combination with osimertinib and should be considered as subsequent-line therapy for patients who progress on osimertinib and develop a HER2 resistance mutation.

Carotuximab effectively reduced the slow-cycling cell population and restored osimertinib sensitivity, offering a promising strategy for managing refractory NSCLC.

The combined contribution of these two positive feedback loops promotes EGFR-TKI resistance in NSCLC. Our findings provide new insight into the role of histone methylation and histone lactylation in TKI resistance. The pivotal NNMT-mediated positive feedback loop may serve as a powerful therapeutic target for overcoming EGFR-TKI resistance in NSCLC.

FYN might delay osimertinib resistance by downregulating the expression of MET, which can be attributed to its active ingredient, Ethyl caffeate.