Publications by authors named "Hyun Cheol Chung"
Article Synopsis
- A study investigated the effectiveness of a combination treatment using lenvatinib and pembrolizumab for patients with advanced triple-negative breast cancer (TNBC) who had not responded to previous chemotherapy.
- In a cohort of 31 patients, the objective response rate was 23% by investigator assessment and 32% by independent review, with higher rates observed in patients with certain biomarkers.
- Despite some encouraging results, 94% of patients experienced treatment-related adverse events, highlighting the need for careful monitoring in future use of this combination therapy.
Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.
Lancet Gastroenterol Hepatol
August 2024
Article Synopsis
- In Asia, adjuvant chemotherapy combined with nivolumab post-gastrectomy is being assessed for effectiveness and safety in treating pathological stage III gastric or gastro-oesophageal junction cancer.
- The ATTRACTION-5 trial involved a randomized, double-blind study across 96 hospitals in East Asia, enrolling patients aged 20-80 with confirmed stage IIIA-C cancer following specific surgeries.
- Patients were divided into two groups to receive either nivolumab with chemotherapy or a placebo with chemotherapy, with the main focus on measuring relapse-free survival and analyzing safety data.
Article Synopsis
- Trastuzumab deruxtecan (T-DXd) showed significant improvement in patients with HER2-positive gastric cancer in the DESTINY-Gastric01 trial, with hints of benefit for those with HER2-low cancer.
- The study faced challenges due to the variability in HER2 expression and genetic alterations in gastric cancer, making it hard to identify which patients would benefit from T-DXd.
- Correlations were found between HER2-associated biomarkers in circulating tumor DNA and objective response rates, indicating potential predictors of effectiveness and the need for further research in larger cohorts.
Objectives: The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort.
Methods: Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy.
Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials And Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled.
Overexpression of transglutaminase 2 (TGase 2; TG2) has been implicated in the progression of renal cell carcinoma (RCC) through the inactivation of p53 by forming a protein complex. Because most p53 in RCC has no mutations, apoptosis can be increased by inhibiting the binding between TG2 and p53 to increase the stability of p53. In the present study, a novel TG2 inhibitor was discovered by investigating the structure of 1H-benzo[d]imidazole-4,7-dione as a simpler chemotype based on the amino-1,4-benzoquinone moiety of streptonigrin, a previously reported inhibitor.
View Article and Find Full Text PDFTrastuzumab is used to treat HER2-amplified metastatic gastric cancer; however, most patients become trastuzumab-resistant within a year. Knowledge of the mechanisms underlying trastuzumab resistance is required to overcome this limitation. Here, we aimed to elucidate this resistance mechanism using four trastuzumab-resistant (TR) cell lines and investigate the efficacy of HER2-targeted therapies to overcome treatment resistance.
View Article and Find Full Text PDFBackground: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC).
Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m or dose level 2, 80 mg/m) on Days 1, 8, 15 every four weeks.
Article Synopsis
- A study investigates the impact of prior antibiotic (pATB) use on the effectiveness of PD-1 inhibitors in patients with advanced gastric cancer (AGC), finding that pATB is linked to poorer progression-free survival (PFS) and overall survival (OS).
- The negative effects of pATB were consistent across multiple patient groups treated with PD-1 inhibitors, while it had no impact on patients receiving irinotecan.
- Analysis reveals that pATB use reduces gut microbiome diversity and alters immune cell profiles, suggesting that caution is needed when prescribing antibiotics to AGC patients who will be treated with PD-1 inhibitors.
Purpose: This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC).
Patients And Methods: Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cβ inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti-PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus-related cases (nivolumab; NIVO cohort).
Background: Evidence for the efficacy of combined PD-1 and HER2 blockade with chemotherapy on progression-free and overall survival in HER2-positive gastro-oesophageal cancer is scarce. The first interim analysis of the randomised, phase 3 KEYNOTE-811 study showed a superior objective response with pembrolizumab compared with placebo when added to trastuzumab plus fluoropyrimidine and platinum-based chemotherapy. Here, we report results from protocol-specified subsequent interim analyses of KEYNOTE-811.
View Article and Find Full Text PDFPurpose: For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers.
Materials And Methods: To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment.
Purpose: BVAC-B is an autologous B cell- and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials And Methods: Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment.
Background: In the randomized, controlled, phase III KEYNOTE-061 trial, second-line pembrolizumab did not significantly prolong overall survival (OS) versus paclitaxel in patients with PD-L1-positive (combined positive score ≥1) advanced gastric/gastroesophageal junction (G/GEJ) cancer but did elicit a longer duration of response and offered a favorable safety profile. This prespecified exploratory analysis was conducted to evaluate associations between tumor gene expression signatures and clinical outcomes in the phase III KEYNOTE-061 trial.
Methods: Using RNA sequencing data obtained from formalin-fixed, paraffin-embedded baseline tumor tissue samples, we evaluated the 18-gene T-cell-inflamed gene expression profile (TcellGEP) and 10 non-TcellGEP signatures (angiogenesis, glycolysis, granulocytic myeloid-derived suppressor cell (gMDSC), hypoxia, monocytic MDSC (mMDSC), MYC, proliferation, RAS, stroma/epithelial-to-mesenchymal transition/transforming growth factor-β, WNT).
Article Synopsis
- Trastuzumab, ramucirumab, and paclitaxel were assessed as a second-line treatment for HER2-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer after failure of first-line trastuzumab therapy.
- In a study involving 50 patients, the combination yielded a median progression-free survival of 7.1 months and an overall survival of 13.6 months, with a significant objective response rate of 54%.
- The safety profile of the treatment was manageable, with no major dose-limiting toxicities noted and loss of HER2 expression seen in 34.8% of patients post-first-line treatment, but without a clear link to treatment outcomes.
Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments.
View Article and Find Full Text PDFBackground: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.
Methods: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Background: The acute palliative care unit (APCU) bridges between active cancer treatment and hospice care. However, no study has proven the efficacy of APCU in Korea.
Objective: To evaluate the first-year outcomes of the patients admitted to an APCU at a tertiary hospital in Korea.
Article Synopsis
- The KEYNOTE-062 study assessed the effectiveness of first-line pembrolizumab alone or with chemotherapy compared to chemotherapy alone for advanced gastric cancer in patients with a certain biomarker (PD-L1 combined positive score ≥1) in Asia.
- Results showed that patients receiving pembrolizumab had longer median overall survival than those on chemotherapy, with improvements noted in both PD-L1 score populations (≥1 and ≥10).
- However, the treatment-related adverse event rates were significantly higher for combination therapies, highlighting a need for careful consideration of side effects when selecting treatments.