Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Purpose: This post-marketing surveillance (PMS) study was conducted to monitor the usage of axitinib (Inlyta) in clinical practice of Korean patients with advanced renal cell carcinoma (RCC) with disease progression during or after a prior systemic therapy in real world. Materials and Methods: In this multicenter, observational study, patients indicated for oral axitinib 5 mg twice daily as second-line therapy for advanced RCC were followed up under routine clinical practices, and their safety and effectiveness outcomes were collected. Results: Between 2012 and 2021, 125 patients were enrolled, and data from 111 patients were analyzed. Median age was 65 years (range, 30 to 84 years), 81% was male, and 110 (99%) had clear cell RCC. The median daily dose of axitinib was 10 mg (range, 4.36 to 15.95 mg) with a median administration period of 5.6 months (range, 15 to 750 days). Eighty-three percentage of patients experienced any grade of adverse events, 71% of which were related to study treatment, including diarrhea (36%), hypertension (21%), stomatitis (17%), decreased appetite (14%), palmar-plantar erythrodysesthesia syndrome (12%), and asthenia (11%). Most adverse events were generally well tolerated and manageable, with 13% of grade ≥ 3. Axitinib dose reduction was required in 20% of the adverse events and discontinuation in 8%. Median progression-free survival was 12.4 months (95% confidence interval [CI], 9.6 to 18.9). Objective responses were observed in 30% of patients (95% CI, 21 to 39) with 4% of complete response and 26% of partial response. Conclusion No new safety signal was found in the present PMS study of Korean RCC patients. Axitinib showed consistent outcomes in terms of effectiveness and safety confirming that the drug is a valid option for second-line therapy in patients with advanced RCC in a real-world setting.

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). Conclusions After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Background: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). Methods: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. Results: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment,AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. Conclusion VT can be considered as an adjustment factor for risk assessment in the secondtrimester serum screening test.

Background/Aims: The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. Methods: A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. Results: Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. Conclusions A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea

Background/Aims: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. Methods: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. Results: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. Conclusions This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Background: People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. Methods: We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. Results: Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. Conclusion Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Background/Aims: Atrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting. Methods: This was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries. Results: A total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively. Conclusions This study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.