EGFR mutation

P2, N=100, Recruiting, The University of Sydney | Not yet recruiting --> Recruiting

P1, N=18, Not yet recruiting, Duke University | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Ner-G was charactered by low immune infiltration levels, stromal contents, tumor mutation burden, copy number alterations, DNA repair activity, cell proliferation, epithelial-mesenchymal transformation, stemness, intratumor heterogeneity, androgen receptor expression and EGFR, PTEN, NF1 and MUC16 mutation rates, while high enrichment of neurons and nervous system pathways, and high tumor purity, estrogen receptor expression, IDH1 and CIC mutation rates, temozolomide response rate and overall and disease-free survival rates...Furthermore, the abundance of neurons is positively associated with clinical outcomes in gliomas, while the enrichment of immune and stromal cells has a negative association with them. Our classification method provides new insights into the tumor biology of gliomas, as well as clinical implications for the precise management of this disease.

Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion.

The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.

Together, this approach offers a potential treatment strategy for patients with EGFRm-driven NSCLC that have a sub-optimal response, or develop resistance, to osimertinib through PIK3CA/AKT/PTEN alterations.

We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Osimertinib has become the first globally accessible third-generation EGFR inhibitor, representing one of the most advanced developments in non-small-cell lung cancer (NSCLC) therapy...These degraders compared with EGFR inhibitors showed better efficiency in their cellular potency, inhibition, and toxicity profiles. In this review, we first introduce the structural properties of EGFR, the resistance, and mutations of EGFR, and then mainly focus on the recent advances of EGFR-targeting degraders along with its advantages and outstanding challenges.

P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025

P1, N=0, Withdrawn, M.D. Anderson Cancer Center | N=60 --> 0 | Trial completion date: Dec 2025 --> Apr 2024 | Active, not recruiting --> Withdrawn | Trial primary completion date: Dec 2025 --> Apr 2024

The first U.S. food and drug administration (US FDA) approval of the imatinib tyrosine kinase inhibitor in 2001 paved the way for nearly 100 small-molecule anti-cancer drugs approved by the US FDA and the national medical products administration (NMPA)...Accumulating evidence has enabled scientists and clinicians to strategize the therapeutic approaches of targeting cancer cells and to navigate the development of drug resistance through the continuous monitoring of tumor evolution and oncogenic adaptations. In this review, we highlight the emerging aspects of Hippo signaling in cross-talk with other oncogenic drivers and how this information can be translated into combination therapy to target a broad range of aggressive tumors and the development of drug resistance.

Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation...Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1...Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.

This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.

These data suggest that high-grade gliomas developed in adult patients with LFS may be involved in pHGG H3-/IDH-wt. PDGFRA and homozygous alterations in TP53 may play pivotal roles in the development of this type of glioma in adult patients with LFS.

Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

P=N/A, N=4000, Recruiting, Sophia Genetics SAS | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Aug 2023 --> Dec 2024

NSCLC w/EGFRex19del & MET amp: durable intracranial + systemic response to amivantamab/osimertinib.

The cancers demonstrated a high rate of epidermal growth factor receptor (EGFR) mutation (69.2%). Persistent GGNs in breast cancer patients with high-risk factors should be adequately monitored for early detection and treatment of lung cancer.

This could impact their function and alter ERRα expression. These insights from MDS enhance our understanding of the structural and dynamic consequences of the L385P ESRRA variant and provide valuable implications for subsequent therapeutic considerations and targeted interventions.

The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Overall, these findings contribute to our understanding of DTP heterogeneity seen after osimertinib treatment and provide insights into potential therapeutic targets. See related article by Hu et al., p. 1303.

Overall, test performance was equally robust with either blood collection tube, eg, regarding limit of detection, linearity, and reproducibility, making Roche cfDNA tubes suitable for routine clinical laboratory use in this setting. Importantly, the Roche cfDNA tubes provided more flexibility for specimen handling versus K2EDTA tubes, eg, in terms of tube mixing, plasma separation, and sample stability, and do not require processing of blood within 8 hours thereby increasing the reach of plasma biopsies in NSCLC.

The OS and CNS-PFS of patients who received upfront LT for BMs followed by osimertinib were significantly longer than those of patients who received osimertinib alone. Upfront LT for BMs may be beneficial in patients with EGFR-mutant NSCLC treated with osimertinib.

In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with an EGFR exon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with an EGFR D770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.

Besides, there is also a subtype of EGFR mutations, known as EGFR 20 exon insertion (EGFR 20ins) mutation. The authors summarized the treatment of a lung adenocarcinoma patient with EGFR 20ins mutation accepting Furmonertinib mesylate, in order to provide effective references for clinical diagnosis and treatment..

Consequently, their detection allows for the selection of emerging treatment options to significantly improve patients' outcomes in these particular subgroups of EGFR-mutated advanced non-small cell lung cancer (NSCLC). Specifically, this commentary is focused on the notable progress of the Phase 3 PAPILLON study that showed primary efficacy results from amivantamab, a bispecific antibody with specific binding and affinity to extracellular domains of EGFR and MET, plus chemotherapy in the first-line setting for EGFR exon 20 insertion-mutated advanced or metastatic NSCLC patients, as compared with chemotherapy alone, thus becoming the new standard of care in this group of patients.

Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.

PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY. In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.

The median overall survival times were 42.86, 66.07, and 41.14 weeks for amplified, highly polysomic, and nonamplified, respectively, and were not significantly different (p =  0.3410). High chromosome 7 polysomic gliomas are rare but our data suggest that they may be biologically similar to nonamplified gliomas.

Persistence of the T790M gene mutation after the development of Osimertinib resistance is associated with higher therapeutic benefits of Osimertinib in NSCLC patients. The results of tissue detection are more significant than those of plasma detection.

P2, N=88, Not yet recruiting, SWOG Cancer Research Network | Initiation date: Feb 2024 --> May 2024

The registration No. is CTR20201933, and the date of registration is 2020-10-16).

There was no significant difference between the LT and TKI groups (P=0.473) regarding the incidence of grade 3 or higher adverse events. This study suggests that the strategic use of additional LT before disease progression is a promising approach for the treatment of EGFR-mutated advanced NSCLC.

No abstract available

Therefore, based on the reported status of immunotherapy combined with chemotherapy for advanced NSCLC, this study conducted a comprehensive literature review by searching keywords "PD-1 and PD-L1, immune checkpoint inhibitor (ICI), and NSCLC" in MEDLINE, major conferences, and major clinical research projects to elucidate the therapeutic efficacy of immunotherapy combined with chemotherapy as the current first-line treatment approach for various types of NSCLC patients. Additionally, it addresses several pressing challenges associated with immunotherapy combined with chemotherapy, including enhancing treatment response and survival rate in specific patient populations and identifying potential biomarkers.

Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

The developed habitat-based radiomics model can be used to accurately predict the EGFR mutation subtypes, which may potentially guide personalized treatments for NSCLC patients with BM.

Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: May 2026 --> Dec 2024

P4, N=60, Recruiting, Maastricht University Medical Center | Not yet recruiting --> Recruiting

In addition, the above clinicopathological characteristics and HER2 IHC results can be valuable determinants for identifying patients with HER2-altered NSCLC. These insights hold promise for the development of more effective diagnostic and therapeutic strategies for this complex subset of NSCLC patients.