This review summarized the results of clinical trials in 2024 that were believed to have a significant impact on clinical practice in the field of gynecologic oncology. The SHAPE trial, INTERLACE and KEYNOTE-A18 trials, and BEATcc and COMPASSION-16 trials were included in early-stage, locally advanced, and recurrent/metastatic cervical cancer, respectively. For uterine corpus cancer, updated survival data of the four trials (NRG-GY018, RUBY, AtTEnd, DUO-E) for endometrial cancer and the first survival data of LMS-04 trial for leiomyosarcoma were described. For ovarian cancer, the final overall survival results of PRIMA study were followed by DUO-O, ATHENA-combo, and FIRST-ENGOT-OV44 trial in different disease conditions. Finally, the results of DESTINY-PanTumor02, a basket trial of trastuzumab deruxtecan, were briefly addressed.

This review summarized the results of clinical trials in 2024 that were believed to have a significant impact on clinical practice in the field of gynecologic oncology. The SHAPE trial, INTERLACE and KEYNOTE-A18 trials, and BEATcc and COMPASSION-16 trials were included in early-stage, locally advanced, and recurrent/metastatic cervical cancer, respectively. For uterine corpus cancer, updated survival data of the four trials (NRG-GY018, RUBY, AtTEnd, DUO-E) for endometrial cancer and the first survival data of LMS-04 trial for leiomyosarcoma were described. For ovarian cancer, the final overall survival results of PRIMA study were followed by DUO-O, ATHENA-combo, and FIRST-ENGOT-OV44 trial in different disease conditions. Finally, the results of DESTINY-PanTumor02, a basket trial of trastuzumab deruxtecan, were briefly addressed.

This review summarized the results of clinical trials in 2024 that were believed to have a significant impact on clinical practice in the field of gynecologic oncology. The SHAPE trial, INTERLACE and KEYNOTE-A18 trials, and BEATcc and COMPASSION-16 trials were included in early-stage, locally advanced, and recurrent/metastatic cervical cancer, respectively. For uterine corpus cancer, updated survival data of the four trials (NRG-GY018, RUBY, AtTEnd, DUO-E) for endometrial cancer and the first survival data of LMS-04 trial for leiomyosarcoma were described. For ovarian cancer, the final overall survival results of PRIMA study were followed by DUO-O, ATHENA-combo, and FIRST-ENGOT-OV44 trial in different disease conditions. Finally, the results of DESTINY-PanTumor02, a basket trial of trastuzumab deruxtecan, were briefly addressed.

Background: Linezolid has been widely used in the treatment for multidrug-resistant tuberculosis. However, there are limitations to use it such as long treatment, because of related side effects, even adequate treatment period has been needed for remission of multidrug-resistant tuberculosis (MDR-TB). Method: The meta-analysis was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. To choose literatures, systematic literature reviews were conducted with databases of PubMed, Web of Science, and EMBASE. Results: Efficacy and safety of Linezolid were determined by 85% (95% CI=79~89%, p<0.05) in the sputum culture conversion and 55% (95% CI=45~64%, p<0.01) in side effects related to linezolid, respectively. In addition, I2 was estimated by 72%. In the subgroup analysis, efficacy and safety by dose and region were analyzed. In the subgroup analysis, compared with the linezolid dose in groups greater than 600 mg/day and less than 600 mg/day, this study showed 85% (95% CI 79~90%, p>0.05) in 206 patients and 82% (95% CI 73~89%, p<0.05) in 297 patients, respectively. Also, in the subgroup analysis, adverse effects caused by linezolid occurred more than 50% of treated patients. Conclusion Therapeutic efficacy of linezolid for MDR-TB patients was confirmed regardless of the initial dose of linezolid, especially for sputum culture conversion and it was recommended that the dose of linezolid has been more effective below 600 mg/day. However, it should be necessary to closely monitored for safety issues since serious side effects possibly occurred by administration of long period treatment.

In healthcare situations, time-to-event (TTE) data are common outcomes. A parametric approach is often employed to handle TTE data because it is possible to easily visualize different scenarios via simulation. Not all pharmacometricians are familiar with the use of non-linear mixed effects models (NONMEMs) to deal with TTE data. Therefore, this tutorial simply explains how to analyze TTE data using NONMEM. We show how to write the code and evaluate the model. We also provide an example of a hands-on model for training.

Objective: The triglyceride-glucose (TyG) index, the product of fasting triglycerides and glucose, is a useful and cost-effective marker of insulin resistance (IR). Furthermore, the TyG index is a known IR screening tool in healthy young adults but not in those with atherosclerotic cardiovascular disease (CVD). Thus, this study aimed to evaluate the TyG index as a predictor of CVD in healthy young adults. Methods: This study enrolled 6,675,424 adults aged 20–39 years without CVD from the National Health Information Database. We categorized them by TyG index quartile from 2009–2017. The study outcomes were stroke, myocardial infarction (MI), and mortality. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates. Results: During a mean 7.4 years of follow-up, 8,506 cases of stroke, 12,312 cases of MI, and 22,667 deaths were recorded. Multivariable-adjusted hazard ratios (HRs) for participants in the highest TyG index quartile demonstrated that they were at higher risk for stroke (HR, 1.253; 95% confidence interval [CI], 1.167–1.346), MI (HR, 1.258; 95% CI, 1.187–1.334), and mortality (HR, 1.151; 95% CI, 1.104–1.200) than those in the lowest TyG index quartile independent of age, sex, smoking, alcohol consumption, physical activity, income, body mass index, blood pressure, and total cholesterol. The HRs for outcomes in the highest quartiles were higher when the TyG index was applied than when triglyceride or fasting glucose alone was applied. Conclusion TyG index, a simple measure reflecting IR, can predict CVD and mortality in young and healthy populations.

Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2-compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

Background: Pembrolizumab, an anti-cancer drug, is known to increase the activity of the immune system, leading to side effects called immune-related adverse events (irAE), including type 1 diabetes. This study analyzed the correlation between blood glucose level and pembrolizumab administration and investigated the covariates that affect those changes in cancer treatment. Methods: The information of 133 adult cancer patients was obtained from the electronic medical record (EMR) to identify the changes in random blood glucose (RBG) levels during the pembrolizumab treatment. Subjects were classified into subgroups according to their baseline RBG level, history of diabetes, and the use of steroids, and linear regression analysis was conducted. In addition, a secondary analysis was performed within the group of subjects having a strong correlation to glycemic change, which was based on the Pearson correlation coefficient being less than -0.7 or greater than +0.7. Univariate and multivariate logistic regressions were conducted to identify the risk factors to glycemic increase. Results: The RBG level tended to descend without significant differences in total patients during the administration period of pembrolizumab. Despite the insignificance, the logistic regression analysis presents that the odds ratios of baseline RBG less than 130 mg/dL, prophylactic steroid use, and higher dose of pembrolizumab per cycle (mg/kg/ cycle) were greater than 1. Conclusions Prophylactic administration of steroids and a higher dose of pembrolizumab per cycle may increase the blood glucose level as irAE in cancer patients with a strong tendency to glycemic change.

Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2-compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

Background: Pembrolizumab, an anti-cancer drug, is known to increase the activity of the immune system, leading to side effects called immune-related adverse events (irAE), including type 1 diabetes. This study analyzed the correlation between blood glucose level and pembrolizumab administration and investigated the covariates that affect those changes in cancer treatment. Methods: The information of 133 adult cancer patients was obtained from the electronic medical record (EMR) to identify the changes in random blood glucose (RBG) levels during the pembrolizumab treatment. Subjects were classified into subgroups according to their baseline RBG level, history of diabetes, and the use of steroids, and linear regression analysis was conducted. In addition, a secondary analysis was performed within the group of subjects having a strong correlation to glycemic change, which was based on the Pearson correlation coefficient being less than -0.7 or greater than +0.7. Univariate and multivariate logistic regressions were conducted to identify the risk factors to glycemic increase. Results: The RBG level tended to descend without significant differences in total patients during the administration period of pembrolizumab. Despite the insignificance, the logistic regression analysis presents that the odds ratios of baseline RBG less than 130 mg/dL, prophylactic steroid use, and higher dose of pembrolizumab per cycle (mg/kg/ cycle) were greater than 1. Conclusions Prophylactic administration of steroids and a higher dose of pembrolizumab per cycle may increase the blood glucose level as irAE in cancer patients with a strong tendency to glycemic change.