Publications by authors named "Yi Long Wu"

Article Synopsis
  • Lung cancer is the most common type of cancer in the Asia-Pacific region, with non-small cell lung cancer (NSCLC) making up about 85% of cases, and a significant mutation rate of 40-60% in Asian patients with lung adenocarcinoma.
  • Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) have improved treatment for NSCLC with mutations, but managing resistance to these drugs is still a major issue with no standardized guidelines.
  • A set of recommendations has been developed, integrating international guidelines and regional clinical experiences, to help healthcare providers classify resistance, conduct clinical testing, and devise treatment strategies for patients struggling with resistance to third-generation EGFR-TKIs.
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Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA -mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation.

Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and (exon 19 deletion or L858R) mutations were enrolled in this observational study.

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Background: The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment.

Methods: We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18-75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs.

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Background: Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC.

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Background: Epidermal growth factor receptor () and mesenchymal-epithelial transition () gene mutations are well established in the pathogenesis of non-small cell lung cancer (NSCLC). However, there is limited understanding about the impact of rare variants, such as exon 20 insertion mutation (ex20ins) and exon 14 skipping mutation (ex14) in the Chinese population even though targeted therapies have been approved in China. We conducted a scoping review to assess the current available evidence of these two mutations in NSCLC in the Chinese population.

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Article Synopsis
  • * Results showed that a higher PRS was more strongly related to EGFR-positive LUAD cases (OR=8.63) than to EGFR-negative cases (OR=3.50), indicating a significant association based on mutation status.
  • * These findings imply that genetic susceptibility to LUAD differs in never-smoking East Asian women depending on whether the cancer has specific mutations, which could affect public health strategies and clinical practices.*
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Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic NSCLC (mNSCLC [EGFR/ALK wild type]) with programmed cell death ligand 1 (PD-L1) tumor cell (TC) membrane expression status of 25% or higher. We report the final analysis of PEARL.

Methods: Adults (N = 669) with previously untreated stage IV mNSCLC were randomized (1:1) to durvalumab 20 mg/kg every four weeks or chemotherapy every three weeks for four to six cycles.

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Introduction: Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation.

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Article Synopsis
  • Zorifertinib is an experimental cancer drug that targets mutations in the EGFR gene and has shown effectiveness in patients with lung cancer that has spread to the brain.
  • A phase 3 trial compared zorifertinib to standard treatments and found that it significantly extended the time patients lived without the disease worsening (progression-free survival).
  • Results indicate that zorifertinib may be a better first-line treatment option for non-small cell lung cancer due to its ability to improve survival and manage side effects effectively.
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Article Synopsis
  • The Eastern Asia region is witnessing significant advancements in targeted drug development, particularly in cancer treatment, driven by technology and medical research improvements.* -
  • There's a focus on personalized medicine, with ongoing clinical trials tailored to the genetic diversity of patients, backed by strong government and enterprise support for innovation and international collaboration.* -
  • The paper discusses genetic testing, drug approvals, and promising lung cancer trials, highlighting key factors that could shape the future of the targeted drug market in Eastern Asia.*
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What Is This Study About?: This is a summary of the results of an ongoing study called CROWN. In the CROWN study, researchers looked at the effects of two medicines called lorlatinib (Lorbrena) and crizotinib (Xalkori) for people with advanced non-small cell lung cancer (NSCLC) who had not been treated yet. Everyone in the study had changes in a called anaplastic lymphoma kinase, or , in their cancer cells.

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Article Synopsis
  • IBI351 is an irreversible, covalent inhibitor specifically targeting the KRAS G12C mutation in advanced solid tumors, particularly among Chinese patients, addressing unmet clinical needs even after FDA-approved therapies exist.
  • In a clinical study involving 176 patients, various doses of IBI351 were tested, with the recommended dose set at 600 mg taken twice daily, showing no major toxic effects while still being effective.
  • The treatment demonstrated a 45.5% overall response rate in patients with non-small cell lung cancer, with promising results, including a 9.6-month median progression-free survival at the optimal dosage.
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Background: Primary lung cancer is the leading cause of cancer-related death worldwide. Common metastatic sites include the brain, liver, bones, and adrenal glands. However, gastric metastases from lung cancer are rare.

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Introduction: An increasing number of early-stage lung adenocarcinomas (LUAD) are detected as lung nodules. The radiological features related to LUAD progression warrant further investigation. Exploration is required to bridge the gap between radiomics-based features and molecular characteristics of lung nodules.

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Article Synopsis
  • Transformation to small cell lung cancer (SCLC) is a resistance mechanism seen in lung adenocarcinoma (LUAD) patients treated with tyrosine kinase inhibitors, particularly in those with leptomeningeal metastases (LM).
  • In a study of 237 non-small cell lung cancer (NSCLC) patients who had lumbar punctures, SCLC cells were identified in the cerebrospinal fluid (CSF) of 8 patients, all of whom showed resistance to targeted therapies.
  • The results suggest that SCLC transformation in CSF can be detected using cytological evaluation and ctDNA analysis, providing valuable insights into treatment resistance mechanisms, with this transformation correlating with reduced survival rates.
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Objectives: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified.

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Introduction: KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study.

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Article Synopsis
  • * Single-cell RNA sequencing revealed that LMs contain diverse macrophage populations with stronger immunosuppressive characteristics, particularly a subset linked to osimertinib resistance influenced by Midkine (MDK).
  • * Elevated MDK levels in cerebrospinal fluid and plasma correlate with worse patient outcomes, suggesting MDK and the RNASE1_M macrophage subtype could be potential targets for treating LMs in NSCLC patients.
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Background: Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population.

Methods: This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries.

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