- |||||||||| Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
Review, Journal: Lazertinib: a novel EGFR-TKI therapy for non-small cell lung cancer. (Pubmed Central) - Jul 1, 2025
Clinical trials highlight its efficacy as monotherapy and in combination with amivantamab, showing improved progression-free survival and response duration in patients with advanced NSCLC...However, emerging resistance mutations, such as C797S, underscore the need for continued innovation, including combination therapies and fourth-generation TKIs. Future research must address these challenges to optimize treatment outcomes for NSCLC patients.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
A clinically translatable approach for assessing durability of response in tumours in vivo (Poster and Exhibition Hall; Poster Board No EACR25-3121) - Jun 29, 2025 - Abstract #EACR2025EACR_1974;
We have applied the method to several studies evaluating the efficacy of EGFR TKIs and demonstrate that preclinical outcomes recapitulate clinical findings. Our results underscore the utility of this approach in enhancing the predictive power and translational potential of preclinical development.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
A20: a potential target to boost immune checkpoint blockade in EGFR driven lung tumors (Poster and Exhibition Hall; Poster Board No EACR25-2531) - Jun 29, 2025 - Abstract #EACR2025EACR_1955;
Our findings identify A20 as an oncogenic driver in lung cancer. The pronounced T-cell infiltration in A20-deficient tumors, even at later stages, suggests that targeting A20 could be a promising strategy to enhance ICB efficacy in EGFR-mutant lung tumors.
- |||||||||| Xalkori (crizotinib) / Pfizer, Tagrisso (osimertinib) / AstraZeneca, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Combined oncogene and pyruvate dehydrogenase kinase inhibition enhances tumor response in resistant NSCLC cells (Poster and Exhibition Hall; Poster Board No EACR25-0655) - Jun 29, 2025 - Abstract #EACR2025EACR_1821;
In parallel, dichloroacetate (DCA), a small molecule that alters cancer cell metabolism by inhibiting pyruvate dehydrogenase kinase (PDK), has been investigated for its potential to reverse the Warburg effect and reprogram tumor cell metabolism...Consequently, EGFR-mutant H1975, c-MET amplified H1993 and KRAS-mutant A549 NSCLC cells, were treated with TKIs (osimertinib, crizotinib and selumetinib, respectively), DCA alone or in combination with TKIs (halved dose)... Our findings indicate that the combination of TKIs and DCA, at low doses, represents a promising therapeutic approach to overcome resistance and improve clinical outcomes in target cancer therapy.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Glucocorticoid Receptor: An Oncosuppressor 'Immune-dependent' in EGFR-driven Lung Adenocarcinoma (Poster and Exhibition Hall; Poster Board No EACR25-2187) - Jun 29, 2025 - Abstract #EACR2025EACR_1628;
We identified tumor intrinsic GR signaling as an powerful tumor suppressor in EGFR driven LUAD, with its loss resulting in a tumor promoting tumor microenvironment. These findings may have major impact on current treatment strategies, including the outcome of osimertinib therapy.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Increased Sensitivity to BCL-2 Inhibition in EGFR-TKI Resistant NSCLC Cell Lines (Poster and Exhibition Hall; Poster Board No EACR25-1105) - Jun 29, 2025 - Abstract #EACR2025EACR_1553;
We find that RTKi resistant NSCLC cell lines show increased sensitivity towards inhibition of Bcl-2 proteins and that RTKi resistance of NSCLC cells is overcome through inhibition of these proteins by specific Bcl-2 inhibitors. These findings represent a general therapeutic approach that relies on the simultaneous blockade of driver mutation mediated EGFR activity and survival-promoting Bcl-2 proteins.
- |||||||||| Mekinist (trametinib) / Novartis, BeOne Medicines, Tagrisso (osimertinib) / AstraZeneca
SOS1 inhibition enhances the efficacy of and delays resistance to oncogene-targeted therapies in lung adenocarcinoma (Poster and Exhibition Hall; Poster Board No EACR25-1617) - Jun 29, 2025 - Abstract #EACR2025EACR_1276;
Our data present a framework for rapidly evaluating and selecting optimal combinations therapies prior to moving into extensive longitudinal pre-clinical animal studies. Our data further show that targeting proximal RTK signaling in combination therapy using a SOS1 inhibitor is a potential strategy to prolong the effectiveness of oncogene-targeted therapies for a majority of LUAD patients.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
The Role of AP-1 Target Transcript Vav3.1 in the Regulation of Osimertinib Resistance in Lung Adenocarcinoma (Poster and Exhibition Hall; Poster Board No EACR25-1999) - Jun 29, 2025 - Abstract #EACR2025EACR_1185;
Our findings highlight the complexity of VAV3.1's involvement in drug resistance that could stem from the polyclonal nature and heterogeneity of our cells. Ongoing experimental strategies aim to further investigate the precise role of VAV3.1 in resistance mechanisms for a more comprehensive understanding of its function.
- |||||||||| Mekinist (trametinib) / Novartis, BeOne Medicines, Tagrisso (osimertinib) / AstraZeneca
Decoding EGFR-Driven Transcriptional Networks in NSCLC (Poster and Exhibition Hall; Poster Board No EACR25-1568) - Jun 29, 2025 - Abstract #EACR2025EACR_899;
This comprehensive mapping of EGFR-driven transcriptional networks will enhance our understanding of resistance mechanisms, identify novel drug targets beyond kinase inhibitors, and may inform rational drug repurposing strategies. Future applications include exploring tissue-specific variations in EGFR-TF networks across cancer types and crosstalk between receptors.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Single-cell transcriptomics identifies vulnerabilities of osimertinib ex-vivo persister cells (Poster and Exhibition Hall; Poster Board No EACR25-2332) - Jun 29, 2025 - Abstract #EACR2025EACR_392;
The understanding of cellular heterogeneity is key to better understand combinatorial treatments. In our preclinical model, a specific subpopulation of DTPs was eliminated by combinatorial treatment which resulted in reduction in the heterogeneity of the resulting DTP population and ultimately in delayed re-growth of tumours.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Targeting low fidelity polymerases to prevent acquired resistance mutations to EGFR-targeted therapy in lung cancer. (Poster and Exhibition Hall; Poster Board No EACR25-0764) - Jun 29, 2025 - Abstract #EACR2025EACR_342;
If our promising preliminary results of TLS inhibition preventing resistance mutations will be confirmed, in vivo PDX studies will be performed to further assess the efficiency of JH-RE06 to prevent relapses in NSCLC. This work will pinpoint new opportunities for drug development to overcome the current major drawback of anti-EGFR therapy and will overall aid in improving lung cancer patients' survival outcomes.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Review, Journal: Traditional Chinese Medicines as Anticancer Agents for Non-Small Cell Lung Cancer with EGFR Mutations: A Review. (Pubmed Central) - Jun 27, 2025
Osimertinib is currently the first-line treatment choice for patients with EGFR L858R/T790M mutations, however, as to other EGFR-TKIs, resistance inevitably occurs...TCM achieves these effects by regulating multiple signaling pathways and mechanisms, while also exhibiting synergistic interactions with EGFR tyrosine kinase inhibitors (TKIs). This review highlights the mechanisms through which TCM influences NSCLC patients harboring EGFR mutations, offering a promising therapeutic strategy for those with EGFR-TKI resistance.
- |||||||||| cisplatin / Generic mfg., Tagrisso (osimertinib) / AstraZeneca
Journal: Anticancer Treatment Influences TREM2 in Tumor-Associated Macrophages in Lung Cancer. (Pubmed Central) - Jun 27, 2025
These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Given TREM2's central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.
- |||||||||| Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca
Journal: Two Cases of Amivantamab-Induced Pneumonitis in Patients With NSCLC: Case Report. (Pubmed Central) - Jun 26, 2025
Although drug-induced interstitial lung disease has been reported with cancer-directed antibody-drug conjugates and EGFR tyrosine kinase inhibitors, it remains a rare event in patients treated with amivantamab. In this report, we present two cases of suspected amivantamab-related drug-induced interstitial lung disease in patients with canonical EGFR mutant NSCLC after progression on osimertinib.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Clinical, Review, Journal: Time-to-Event Modeling for Survival Prediction of Osimertinib as the First- and Second-Line Therapy. (Pubmed Central) - Jun 26, 2025
Subgroup analysis revealed longer estimated 3- and 5-year survival rates for non-Asian patients compared to Asian patients (60% vs. 49% and 29% vs. 21%, respectively). The predicted survival rates from the time-to-event modeling align with the original clinical trial results, and an ethnic difference in Osimertinib efficacy was observed.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, erlotinib / Generic mfg.
Journal: Targeting both wild-type EGFR and its drug-resistant mutants with erlotinib-aptamer conjugates. (Pubmed Central) - Jun 24, 2025
Further in vitro and in vivo studies demonstrate that LY-dE#5 effectively suppresses the growth of EGFR-driven cancer cells. These data indicate that the erlotinib-aptamer conjugate is an efficient pan-EGFR degrader that holds the translational potential for cancer treatment to overcome the common drug-resistance issues of EGFR-TKIs.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Journal: FL30: an epidermal growth factor kinase inhibitor overcoming T790M and C797S mutations through unique conformational modulation mechanism. (Pubmed Central) - Jun 24, 2025
The IC50 comparable to the Osimertinib - one of the most renowned EGFR-TKIs - emphasizes the remarkable success of the design approach...Kinetic studies, molecular modeling, and Plasmon Internal Reflection Surface-Enhanced Infrared Absorption (PIR-SEIRA) microscopy suggests that FL30 binds to the orthosteric site while inducing the transition of the mutant EGFR toward an inactive-like state. These findings highlight FL30's potential for further optimization and propose a novel approach for developing targeted therapies that combine orthosteric binding with allosteric modulation.
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Observational data, Retrospective data, Journal, Real-world evidence: Risk Factors Associated with Suboptimal Real-World Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Treated with Front-Line Recommended Therapy. (Pubmed Central) - Jun 24, 2025
These findings highlight FL30's potential for further optimization and propose a novel approach for developing targeted therapies that combine orthosteric binding with allosteric modulation. More than 90% of the assessed real-world patients with EGFR-mutated (ex19del/L858R) NSCLC who received 1L osimertinib had risk factors associated with suboptimal outcomes, highlighting the urgent unmet need for new treatments and emphasizing the importance of administering the most effective therapy in the 1L setting.
- |||||||||| Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
Journal, Adverse events: Dermatologic Adverse Event Mitigation and Management Strategies with Amivantamab (Pubmed Central) - Jun 22, 2025
It is imperative to note that occipital condyle syndrome signifies the metastasis of a malignancy to the base of the skull, necessitating meticulous observation and management. The MARIPOSA study assessed amivantamab
- |||||||||| Tagrisso (osimertinib) / AstraZeneca
Journal: Case Report: Osimertinib-induced acute interstitial lung disease. (Pubmed Central) - Jun 20, 2025
Despite discontinuation of osimertinib and administration of aggressive supportive care, her clinical condition continued to deteriorate, ultimately resulting in a fatal outcome. This case underscores the importance of monitoring respiratory symptoms in patients receiving EGFR-TKIs, promptly diagnosing ILD, and implementing early intervention to mitigate adverse outcomes.
- |||||||||| Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
Journal: Optimizing management of stage IV EGFR mutant non-small cell lung cancer in Asia: An expert opinion. (Pubmed Central) - Jun 14, 2025
For lazertinib+amivantamab, measures to mitigate adverse events such as the use of pre-medication with steroids, prophylactic anticoagulants, and dose modification are recommended. For patients progressing on one of the combination regimens, experts recommended repeat NGS testing and continued treatment with chemotherapy.
- |||||||||| Rybrevant (amivantamab-vmjw) / J&J, Tagrisso (osimertinib) / AstraZeneca, Lazcluze (lazertinib) / J&J
Review, Journal: Current treatment landscape for patients with non-small cell lung cancer with common EGFR mutations. (Pubmed Central) - Jun 12, 2025
Among EGFR-TKIs, third-generation agents such as osimertinib have shown marked efficacy and favorable safety profiles and have become the standard of care in the first-line setting...Similarly, the MARIPOSA trial demonstrated clinical benefit of the combination of the EGFR-MET bispecific antibody, amivantamab, with the third-generation EGFR-TKI, lazertinib, further supporting the use of combination therapies as first-line treatment for EGFR-mutated NSCLC...Analysis of such biomarkers can facilitate dynamic and personalized therapeutic adjustments, potentially improving outcomes. This review provides a comprehensive overview of the latest clinical evidence supporting therapeutic advances in the management of EGFR-mutated NSCLC, emphasizing the importance of tailoring treatment strategies based on tumor biology, patient-specific factors, and evolving therapeutic options.
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