Publications by authors named "Jih- Hsiang Lee"
Background: D07001-F4 is an absorption-enhanced oral gemcitabine developed in liquid formulation and adjusted to D07001-softgel capsules. We conducted 2 phase 1 studies to evaluate the dose-limiting toxicity (DLT), pharmacokinetics (PK), and maximum tolerated dose (MTD) of the 2 formulations of D07001 in patients with advanced solid tumors.
Materials And Methods: Initially, patients received escalating doses (2-80 mg) of D07001-F4 thrice a week for 2 weeks, followed by 1-week rest.
Background: Distant metastasis is a leading cause of thyroid cancer (TC)-related deaths. Genetic profiling is typically limited to one sample per patient due to cost and sampling-risk concerns. Differences between samples from thyroid and distant metastasis within individual patients are unclear.
View Article and Find Full Text PDFBackground: 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.
Background: Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need.
Methods: We describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20).
Background: The role for radiotherapy or surgery in the upfront management of brain metastases (BrM) in epidermal growth factor receptor mutant (m) or anaplastic lymphoma kinase translocation positive (+) non-small cell lung cancer (NSCLC) is uncertain because of a lack of prospective evidence supporting tyrosine kinase inhibitor (TKI) monotherapy. Further understanding of practice heterogeneity is necessary to guide collaborative efforts in establishing guideline recommendations.
Methods: We conducted an international survey among medical (MO), clinical (CO), and radiation oncologists (RO), as well as neurosurgeons (NS), of treatment recommendations for asymptomatic BrM (in non-eloquent regions) EGFRm or ALK+ NSCLC patients according to specific clinical scenarios.
Factors associated with survival of patients with advanced lung cancer and long travel distances.
J Formos Med Assoc
February 2024
Article Synopsis
- The study examined survival factors for advanced lung cancer patients in Taiwan who traveled long distances for treatment, using data from a large medical database.
- It found that factors such as younger age, female sex, smaller tumor size, and participation in clinical trials were linked to longer survival.
- However, traveling long distances or receiving treatment in medical centers did not independently impact survival rates for these patients.
Anaplastic thyroid cancer (ATC) is a rare but lethal thyroid cancer. Dabrafenib and trametinib has been the standard treatment for the patients with BRAF mutation based on phase II study. This study aimed to exam the impact of dabrafenib and trametinib in ATC patients.
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- The study presents a case of lung cancer where a patient had both a mutation and a rearrangement that developed resistance to EGFR inhibitors.
- Immunohistochemical analysis showed both mutant and ALK fusion proteins present in the same tumor cells, highlighting the complexity of the cancer's genetic profile.
- Findings indicate that using a combination of ALK and EGFR inhibitors may improve treatment outcomes for patients with nonsmall cell lung cancer (NSCLC) exhibiting these concurrent genetic changes.
Article Synopsis
- A definitive diagnosis of pulmonary sarcomatoid carcinoma is challenging with small biopsies, leading to the acceptance of advanced non-small-cell lung cancer with spindle/giant cell characteristics as a diagnosis.* -
- A study of 101 patients revealed that most received systemic therapy, with immune checkpoint inhibitors (ICIs) linked to significantly better overall survival (OS) compared to those who did not receive them (18.2 months vs. 3.8 months).* -
- The presence of high programmed death ligand-1 (PD-L1) expression was associated with better OS, and the findings indicate that though survival is poor for advanced NSCLCsg, ICIs may offer a potential benefit, warranting further research.*
Background: Radiotherapy (RT) and surgery (Sx) are effective in treating brain metastases. However, immune checkpoint inhibitors (ICI) have shown activity against asymptomatic melanoma brain metastases (MBM). BRAF/MEK inhibitors can be used to treat BRAF V600 mutation positive (BRAF+) MBM.
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- Advances in genomic DNA detection from plasma allow tracking of tumor DNA shedding during treatment for non-small cell lung cancer (NSCLC), specifically with the drug osimertinib used for T790M mutations.
- In a study of 15 patients with advanced NSCLC who had previously undergone treatment, it was found that osimertinib led to a 53% objective response rate and a median progression-free survival of 7.3 months.
- The study concluded that the presence of T790M or an increase in activating mutation allelic frequency in circulating tumor DNA four weeks after starting osimertinib may indicate a likely disease progression within 16 weeks.
Article Synopsis
- PD-L1 expression has been linked to clinical outcomes in EGFR mutant lung adenocarcinoma, but its role in ALK-positive lung adenocarcinoma treated with crizotinib was previously unclear.
- In a study involving 78 ALK-positive advanced adenocarcinoma patients, those with PD-L1 0% had better objective response rates and longer progression-free survival compared to those with higher PD-L1 levels.
- The findings suggest that positive PD-L1 expression may indicate poorer clinical outcomes in ALK-positive lung adenocarcinoma patients receiving crizotinib, highlighting the need for personalized treatment approaches.
Background: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers.
Methods: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]).
Article Synopsis
- - The study investigates how PD-L1 expression affects the efficacy and resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with lung adenocarcinoma (ADC) harboring EGFR mutations, highlighting that PD-L1 isn't strongly related to treatment outcomes in these cases.
- - Results from a cohort of 153 Taiwanese patients indicate that those with PD-L1 expression lower than 50% had better response rates and longer progression-free survival when treated with TKIs compared to those with higher PD-L1 expression.
- - The research suggests that lower PD-L1 expression is a significant independent predictor of longer progression-free survival and that higher PD-L1 levels are associated with a reduced likelihood of developing secondary resistance mutations,
Article Synopsis
- The study evaluates the effectiveness of immediate cranial irradiation techniques for patients with EGFR mutant lung cancer and brain metastases, comparing methods like whole brain radiation (WBRT) and stereotactic radiosurgery (SRS).
- Patients receiving SRS showed longer median survival times (55.7 months) compared to those who had WBRT (18.5 months) and the other groups, indicating that SRS may be a better choice for certain patients.
- The findings suggest that treatment should be personalized based on individual patient factors and that immediate WBRT may not be necessary for all patients with brain metastases.
Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d.
View Article and Find Full Text PDFGefitinib, erlotinib and afatinib are approved for first-line treatment of advanced non-small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs.
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- Immunotherapy targeting PD-1 improves treatment outcomes for patients with metastatic non-small cell lung cancer (NSCLC), particularly in those with high PD-L1 expression, but real-world data on its effectiveness and predictive value are limited.
- A retrospective review of 74 NSCLC patients found a median progression-free survival (PFS) of 1.8 months and overall survival (OS) of 7.9 months, with an objective response rate of 32%, revealing that EGFR mutations were linked to poor response while good performance status and smoking history indicated better survival.
- The study concluded that anti-PD-1 therapy shows comparable efficacy and safety in real-world settings compared to clinical trials, and that higher tumor PD-L1 expression may be
Article Synopsis
- The study investigates the link between responses to EGFR tyrosine kinase inhibitors (TKIs) and survival rates in patients with advanced non-small-cell lung cancer with EGFR mutations.
- A total of 98 patients were analyzed, showing that 77% responded positively to treatment, with significant improvements in progression-free survival (PFS) and overall survival (OS) for responders compared to those with stable disease, especially after a longer observation period.
- However, the extent of tumor shrinkage did not correlate with increased survival rates among responders.
The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. After tumor progression, many combination therapy regimens that include an EGFR-TKI, or EGFR-TKI monotherapy, have been tested in prospective trials with the aim of extending survival.
View Article and Find Full Text PDFBackground/purpose: Research biopsies (RBs) are crucial for developing novel molecular targeted agents. However, the safety and diagnostic yields of RBs have not been investigated in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
Methods: We searched the medical records of NSCLC patients who participated in lung cancer clinical trials and underwent mandatory RBs between 2012 and 2014 at our institution.
A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.
Oncotarget
June 2017
Background: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue.
Results: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.
New data on clinical decisions in NSCLC patients with uncommon EGFR mutations.
Expert Rev Respir Med
January 2017
Non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor (EGFR) mutations together account for approximately 10% of all EGFR mutations. The most common of which being G719X, S768I, L861Q, and exon 20 insertions. The clinical significance, particularly their response to EGFR tyrosine kinase inhibitors (TKIs) is largely unclear.
View Article and Find Full Text PDFArticle Synopsis
- First- and second-generation EGFR-TKIs like gefitinib, erlotinib, and afatinib are standard treatments for advanced lung cancer with EGFR mutations.
- Third-generation EGFR-TKIs have been developed to target the common resistance mutation T790M, which affects many patients undergoing 1/2G TKI treatment.
- While 3G EGFR-TKIs have different structures that reduce side effects like skin and gastrointestinal toxicities, they introduce new adverse events that are not seen with earlier generations, and mechanisms of resistance to these newer treatments are still being studied.