Outcomes of patients receiving urgent palliative radiotherapy for advanced lung cancer: an observational study.

Background: There is considerable variability in the management of patients with advanced lung cancer referred for palliative radiotherapy owing to uncertainties in prognosis and the benefit of treatment. This study presents the outcomes of patients seen in the Fast Track Lung Clinic, an urgent access palliative radiotherapy clinic, and aims to identify factors associated with treatment response and survival.

Methods: Consecutive patients with advanced lung cancer seen in the Fast Track Lung Clinic between January 2014 and July 2020 were included.

A patent review of small molecular inhibitors targeting EGFR exon 20 insertion (Ex20ins) (2019-present).

Introduction: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy.

Areas Covered: This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases.

Risk Stratification and Adjuvant Chemotherapy for High-Risk Stage IA Lung Adenocarcinoma: The Unmet Needs.

Introduction: To identify high-risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies.

Methods: Consecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence-free survival (RFS).

CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for non-small cell lung cancer (NSCLC) patients with EGFR mutations; however, drug resistance limits their efficacy. Cytoskeleton-associated protein 4 (CKAP4) has been linked to cancer progression, but its role in EGFR-TKI resistance remains unclear.

Objective: This study investigates the clinical relevance of CKAP4 as a therapeutic target to overcome EGFR-TKI resistance in lung adenocarcinoma (LUAD) patients.

Targeted therapy‑associated cardiotoxicity in patients with stage‑IV lung cancer with or without cardiac comorbidities.

Targeted drugs have revolutionized the treatment of advanced non‑small cell lung cancer (NSCLC). However, the understanding of how cardiac comorbidity and toxicity affect the clinical outcomes of patients following targeted therapy remains limited. In a 14‑year cohort, cardiac comorbidities and toxicities among patients with stage‑IV NSCLC treated with targeted therapy were identified.

Observational study of the efficacy and safety of first-line osimertinib and later treatments for uncommon epidermal growth factor receptor-activating mutation-positive advanced non-small cell lung cancer.

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is a first-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations, including both sensitizing and T790M resistance mutations. Its real-world efficacy against uncommon EGFR mutations remains under-researched.

Methods: The REIWA study, a multicentric, prospective, observational study conducted in Japan from September 2018 to August 2020, enrolled patients with advanced or recurrent EGFR mutation-positive NSCLC receiving osimertinib.

Weight loss in patients on osimertinib for metastatic EGFR-mutant non-small cell lung cancer.

Background: Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes.

Clinical outcomes of patients with EGFR-mutated NSCLC developing interstitial lung disease during first-line osimertinib therapy: a sub-analysis of the Reiwa study.

Introduction: Osimertinib-induced interstitial lung disease in untreated EGFR-mutated, advanced non-small cell lung cancer is being reported at a higher rate in Japan than elsewhere. However, data on the interstitial lung disease incidence during first-line osimertinib therapy and the course of lung cancer treatments administered after interstitial lung disease onset in the real-world setting are scarce.

Materials And Methods: The present study reviewed the data from the Reiwa study, a multicentric, observational study examining the efficacy and safety of first-line osimertinib therapy in the clinical setting.

Methylation-modulated PFTK1 regulates gefitinib resistance via Wnt/β-catenin signaling in EGFR mutant non-small-cell lung cancer cells.

Inevitable gefitinib resistance is the biggest bottleneck in current treatment and the mechanisms are not fully understood. Here, we observe that PFTK1 (also named CDK14) is significantly enhanced in NSCLC with gefitinib resistance. And the upregulation of PFTK1 is negatively associated with progression-free survival (PFS) in NSCLC patients who receive gefitinib treatment.

Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2.

Background: The T790M mutation in the epidermal growth factor receptor (EGFR) gene is the primary cause of resistance to EGFR-tyrosine kinase inhibitor (TKI) therapy in non-small cell lung cancer (NSCLC) patients. Previous research demonstrated that certain traditional Chinese medicine (TCM) monomers exhibit anti-tumor effects against various malignancies. This study aims to investigate the potentials of shikonin screened from a TCM monomer library containing 1060 monomers in killing EGFR-T790M drug-resistant NSCLC cells and elucidate the underlying mechanisms.

Targeting PRMT1 reduces cancer persistence and tumor relapse in EGFR- and KRAS-mutant lung cancer.

Incomplete killing of cancer cells undermines oncogene-targeting therapies and drives disease relapse. Eliminating cancer cells that persist during treatment is crucial for improving treatment outcomes. Here, we discovered that a specific isoform of type I protein arginine methyltransferases (PRMTs), namely PRMT1, enables lung cancer cells with EGFR or KRASG12C driver mutations and high STAT1 activity to persist through targeted drug treatments.

Plasma-Based Comprehensive Genomic Profiling DNA Assays for Non-Small Cell Lung Cancer: A Health Technology Assessment.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all lung cancer cases. While some cases of NSCLC with actionable genomic alterations in the tumour cells may respond to standard therapies, they often show greater improvement with targeted therapies. The current standard of care in Ontario involves testing for actionable genomic alterations using both DNA and RNA panels via tissue testing alone.

Targeting C797S mutations and beyond in non-small cell lung cancer-a mini-review.

Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases and has a high mortality worldwide, however, targeting common epidermal growth-factor receptor (EGFR) alterations (i.e., del19, L858R) has provided a paradigm shift in the treatment of NSCLC.

PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma.

Background: The efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.

Methods: Our study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies.

What is the optimal first-line regimen for advanced non-small cell lung cancer patients with epidermal growth factor receptor mutation: a systematic review and network meta-analysis.

Objectives: There are currently various tyrosine kinase inhibitor (TKI)-based regimens available, and it can be challenging for clinicians to determine the most effective and safe option due to the lack of direct comparisons between these regimens. In this study, we conducted a network meta-analysis comparing the efficacy and safety of distinct regimens to determine the optimal regimen for patients with EGFR-mutated non-small cell lung cancer, thereby facilitating clinical decision-making.

Materials And Methods: The PubMed, Embase, Cochrane Library databases and international conference databases were comprehensively searched from their inception to 02 April 2024 for collecting data regarding efficacy and safety from eligible randomized controlled trials (RCTs).

Plasma metabolomics profiling of EGFR-mutant NSCLC patients treated with third-generation EGFR-TKI.

Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the latest and a vital treatment option for non-small cell lung cancer (NSCLC) patients. Although EGFR-sensitive mutations are an indication for third-generation EGFR-TKI therapy, 30% of NSCLC patients lack response and all patients inevitably progress. There is a lack of biomarkers to predict the efficacy of EGFR-TKI therapy.

Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer.

The fusion event between EML4 and ALK drives a significant oncogenic activity in 5% of non-small cell lung cancer (NSCLC). Even though potent ALK-tyrosine kinase inhibitors (ALK-TKIs) are successfully used for the treatment of EML4-ALK-positive NSCLC patients, a subset of those patients eventually acquire resistance during their therapy. Here, we investigate the kinase responses in EML4-ALK V1 and V3-harbouring NSCLC cancer cells after acute inhibition with ALK TKI, lorlatinib (LOR).

A Podcast Discussion on the Intracranial Efficacy of Antibody-Drug Conjugates in Patients with EGFR-Mutated NSCLC with Brain Metastases.

The incidence of brain metastases is higher in patients with non-small cell lung cancer (NSCLC) than in patients with most other cancers, and the development of brain metastases is associated with poor prognosis. The objective of the podcast is to provide information about current and future treatments for brain metastases that develop in patients with EGFR-mutated NSCLC. The panel discusses surveillance and management of patients with brain metastases, different types of currently used treatments, and recent data on the intracranial efficacy of antibody-drug conjugates (ADCs).

PD-L1 expression and immune profiling cannot predict osimertinib efficacy in lung cancer with EGFR T790 M mutation: A translational study.

Background: PD-L1 is associated with poor efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in untreated EGFR-mutant non-small-cell lung cancer (NSCLC). Whether PD-L1 is also predictive of osimertinib efficacy in pre-treated patients with an acquired EGFR T790 M mutation is unclear.

Patients And Methods: PD-L1 expression and tumor microenvironments were evaluated in tumors from EGFR-mutant T790 M + NSCLC patients treated with osimertinib.

Decoding the Clinical and Molecular Signatures of EGFR Common, Compound, and Uncommon Mutations in Non-Small Cell Lung Cancer.

Introduction: Epidermal growth factor receptor (EGFR) mutations are key oncogenic drivers in lung adenocarcinoma (LUAD), predominantly affecting Asian, non-smoking, and female populations. While common mutations, such as exon 19 deletions and L858R, respond well to tyrosine kinase inhibitors (TKIs), uncommon EGFR mutations and compound variants exhibit variable treatment responses. This study aims to compare clinical characteristics and molecular profiles of patients with common, uncommon, and compound EGFR mutations, assessing their implications for therapy outcomes.

Utilization of EGFR, ALK, and BRAF Inhibitors in the Treatment of Lung Cancer in Germany.

Background: There is a lack of real-world data on the use of targeted cancer drugs requiring molecular tumor diagnostics in the treatment of lung cancer in Germany.

Aims: We aimed to characterize the use of such drugs in lung cancer patients based on longitudinal analyses.

Methods And Results: Using the GePaRD database (claims data from ~20% of the German population) we identified lung cancer patients diagnosed in 2016 based on a previously developed algorithm and followed them until death, end of continuous insurance, or end of 2019.

Comparison of targeted next generation sequencing assays in non-small cell lung cancer patients.

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer the mutational spectrum of which has been extensively characterized. Treatment of patients with NSCLC based on their molecular profile is now part of the standard clinical care. The aim of this study was firstly to investigate two different NGS-based tumor profile genetic tests and secondly to assess the clinical actionability of the mutations and their association with survival and clinicopathological characteristics.

Postoperative adjuvant therapy with molecularly targeted agents for non-small cell lung cancer.

The efficacy of molecularly targeted agents has been established in advanced lung cancer, and their indications have recently expanded to include perioperative treatment of resectable lung cancer. For epidermal growth factor receptor (EGFR) mutation-positive patients, postoperative adjuvant therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) is available in Japan following the results of the ADAURA trial. In addition to EGFR-TKIs, postoperative adjuvant therapy with TKIs targeting anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) is expected to be established.

Real-World Prevalence, Treatment Patterns, and Outcomes for Patients With HER2 (ERBB2)-Mutant Metastatic Non-Small Cell Lung Cancer, From a US-Based Clinico-Genomic Database.

Objectives: Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC.

Materials And Methods: This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database.

The Effectiveness of Afatinib as First-Line Treatment in Vietnamese Patients With EGFR-Mutant Non-Small Cell Lung Cancer and Brain Metastases.

Introduction: The role of afatinib in the first-line treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC) patients has been proven through clinical trials and real-world studies. However, additional data on the effectiveness of afatinib in patients with brain metastases are lacking.

Methods: EGFR-mutant NSCLC patients with brain metastases were retrospectively reviewed across nine cancer centers in Vietnam from April 1, 2018 to June 1, 2022.