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Clinical pharmacologic aspects of immune checkpoint inhibitors in cancer therapy
김규표,정헌 대한임상약리학회 2016 Translational and Clinical Pharmacology Vol.24 No.1
During the past two years, three immune checkpoint inhibitors, ipilimumab, nivolumab and pembrolizumab, have been approved and revolutionized cancer immunotherapy. Translational and clinical pharmacology of these agents have contributed in identifying patients who will receive benefit, dose effect relationship and surrogate endpoints of clinical benefit. In addition, population pharmacokinetics/pharmacodynamics have facilitated scientific clinical development, which has led to accelerated approval of these agents. This paradigm may show how early phase studies may allow identification of subgroup of patients who can benefit and subsequent approval of drugs based on smaller patient population. This may speed the access of effective treatment for patients with life-threatening diseases.
김규표,김정은,홍용상,안성민,천성민,홍승모,장세진,유창식,김진천,김태원 대한암학회 2017 Cancer Research and Treatment Vol.49 No.1
Purpose Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. Materials and Methods In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry- based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. Results In this study, with OncoMap, mutations were identified in 80.4% of patients with the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. Conclusion These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.
김규표 ( Kyu-pyo Kim ) 대한내과학회 2020 대한내과학회지 Vol.95 No.6
Precision medicine is the modern era version of “personalized medicine”, which integrates data from genomics and clinical information to optimize the care delivered to patients. As next generation sequencing (NGS) revolutionized the speed and cost of genomic sequencing, precision medicine entered clinical practice in 2017 via the national reimbursement of oncology and rare diseases. In parallel, the digitalization of clinical data through electronic health recording (EHR) and hospital information systems has allowed data collection and analysis. This has led to the integration of biomarkers and clinical records, which have introduced precision medicine into clinical practice. Today, many countries and medical institutes are endeavoring to create systems that will enable precision medicine to be applied to clinical practice. These data systems will benefit the patient by providing accurate data based on his/her characteristics rather than the conventional approach of using “average data”. Internal medicine will transform into a data-driven science that enables physicians to translate molecular biomarkers and big data analysis into improved clinical care. (Korean J Med 2020;95:382-386)
김규표 ( Kim Gyu Pyo ),김명환 ( Kim Myeong Hwan ),이윤정 ( Lee Yun Jeong ),송문희 ( Song Mun Hui ),박도현 ( Park Do Hyeon ),이상수 ( Lee Sang Su ),서동완 ( Seo Dong Wan ),이성구 ( Lee Seong Gu ),민영일 ( Min Yeong Il ),송동은 ( So 대한소화기학회 2004 대한소화기학회지 Vol.43 No.2
Background/Aims: Autoimmune pancreatitis is a distinctive type of chronic pancreatitis with reversibility. We analyzed the largest number of patients with autoimmune pancreatitis among the studies carried out at a single institution in Korea. Methods: We retrospectively analyzed the clinical, radiologic, laboratory and histologic features in 17 patients who were diagnosed as autoimmune pancreatitis. Results: The patients were predominately elderly men who presented with jaundice or nonspecific gastrointestinal symptoms. In most of the patients, serum pancreatic enzymes were normal or mildly elevated with an accompanying cholestatic biochemical profile. Elevated IgG levels and detection of autoantibodies were observed in 47% (8/17) and 35% (6/17), respectively. Thirteen patients showed histologic findings of lymphoplasmacytic infiltration and fibrosis, and one patient showed predominant infiltration of eosinophils. Fifteen patients revealed radiologic images of diffuse swelling of pancreas and the sclerosing pattern on direct pancreatogram. All of the features improved in response to oral steroid therapy. Two cases showed focal narrowing with upstream duct dilatation and thus, they were diagnosed as focal type. Diabetes mellitus concurred in 13 cases and primary sclerosing cholangitis and Sjoren`s syndrome were present in 1 case, respectively. Conclusions: The recognition of autoimmune pancreatitis allows patients to avoid unnecessary surgery and recover with the administration of oral steroid. (Korean J Gastroenterol 2004; 43:112-119)
Regorafenib as Salvage Treatment in Korean Patients with Refractory Metastatic Colorectal Cancer
김승태,김태원,김규표,김태유,한세원,이지연,임성희,이민영,김해수,박영석 대한암학회 2015 Cancer Research and Treatment Vol.47 No.4
Purpose Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standardof care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, thereare no data on this drug in Korean patients. Materials and MethodsWe evaluated patients who received oral regorafenib 160 mg once daily during the first 3weeks of each 4-week cycle between August 2013 and September 2013. All patients hadpreviously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agentssuch as cetuximab or bevacizumab. ResultsThirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; EasternCooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). Theoverall response rate was 3.1% and the disease control rate was 50.0% (95% confidenceinterval [CI]) with one partial response and 15 patients with stable disease. The medianprogression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the medianoverall survival has not yet been reached. The most common adverse events of grade twoor higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%),abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicitiesincluded LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia(3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death. ConclusionRegorafenib appears to have promising activity and tolerable toxicity profiles in Koreanpatients with refractory CRC, consistent with the CORRECT trial findings.
임동훈,윤현석,김규표,류백열,이상수,박도현,송태준,황대욱,이재훈,송기병,김송철,홍승모,형재원,유창훈 대한암학회 2023 Cancer Research and Treatment Vol.55 No.4
Purpose There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). Materials and Methods Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. Results Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. Conclusion Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.