Patency of Drug-Coated versus Conventional Balloon Angioplasty for Hemodialysis Access Stenosis

Purpose: This study aimed to evaluate the post-intervention target primary patency of drug-coated balloon angioplasty (DCBA) compared with conventional balloon angioplasty (CBA) in the treatment of the dysfunctional autogenous arteriovenous fistula (AVF) in a real-world clinical setting. Materials and Methods: This retrospective study included 24 patients with end-stage renal disease, who developed dysfunctional AVF during hemodialysis, and underwent endovascular treatment using CBA and DCBA from January 1, 2014, to June 30, 2021. The demographic data of patients and details regarding their fistula were recorded. Post-intervention target primary patency was analyzed. Results: Sixteen men and 8 women with an average age of 63.9 ± 14.2 years, who underwent 333 endovascular treatments in 57 target lesions of access were enrolled. DCBA was a protective factor for the treatment of a target lesion of dysfunctional access with an adjusted hazard ratio of 0.725 (95% confidence interval [CI]: 0.528–0.996; P = 0.047). According to the Weibull proportional hazards regression model, DCBA showed a longer post-intervention target primary patency than CBA. Conclusion: DCBA has better outcomes in terms of post-intervention target primary patency in the real-world treatment of dysfunctional autogenous AVF

O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC

BackgroundPD-L1/PD-1 inhibitors (CPI) as monotherapy or in combination with platinum-based doublet chemo (± bevacizumab) are 1L treatment options in metastatic NSCLC, with choice of agent(s) determined by PD-L1 expression. For patients (pts) who may be ineligible for combination therapy, CPI monotherapy remains an attractive treatment choice. IMpower110 evaluated atezo as 1L treatment in PD-L1–selected pts independent of tumor histology.MethodsIMpower110 enrolled 572 chemo-naive pts with stage IV nonsquamous (nsq) or squamous (sq) NSCLC, PD-L1 expression ≥ 1% on TC or IC, measurable disease by RECIST 1.1 and ECOG PS 0-1. Pts were randomized 1:1 to receive atezo 1200 mg IV q3w (Arm A) or platinum-based chemo (Arm B; 4 or 6 21-day cycles). Arm B nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed 500 mg/m2 IV q3w; Arm B sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Stratification factors were sex, ECOG PS, histology and tumor PD-L1 status (TC1/2/3 and any IC vs TC0 and IC1/2/3). The primary endpoint of OS is tested hierarchically in the wild-type (WT; EGFR/ALK-negative) population (TC3 or IC3 then TC2/3 or IC2/3 then TC1/2/3 or IC1/2/3).ResultsThe 3 primary efficacy populations included 554 TC1/2/3 or IC1/2/3 WT pts, 328 TC2/3 or IC2/3 WT pts and 205 TC3 or IC3 WT pts. Median follow-up was 15.7 months (range, 0-35) in TC3 or IC3 WT pts. In the TC3 or IC3 WT population, atezo monotherapy improved median OS by 7.1 months (HR, 0.595; P = 0.0106) compared with chemo (table 1). The safety population comprised 286 pts in Arm A and 263 in Arm B. Treatment-related AEs (TRAEs) and Grade 3-4 TRAEs occurred in 60.5% (Arm A) and 85.2% (Arm B), and 12.9% (Arm A) and 44.1% (Arm B), respectively.Abstract 081 Table 1ConclusionsAt this interim analysis, IMpower110 met the primary endpoint of OS with statistically significant and clinically meaningful improvement in the TC3 or IC3 WT population. The safety profile favored Arm A, with no new or unexpected safety signals identified.Trial RegistrationNCT02409342Ethics ApprovalThe trial was conducted according to the principles of the Declaration of Helsinki. All patients provided written informed consent. Protocol approval was obtained from independent review boards or ethics committees at each site

Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6)

Introduction: In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported. Patients and Methods Lung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory. Results: Compared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations. Conclusions: These exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups. Electronic supplementary material The online version of this article (10.1007/s40271-017-0287-z) contains supplementary material, which is available to authorized users

การศึกษาต้นทุนอรรถประโยชน์ ยาภูมิคุ้มกันมะเร็งในผู้ป่วยมะเร็งปอดชนิดเซลล์ไม่เล็กที่กลับเป็นซ้ำหลังจากได้รับการรักษายาเคมีบำบัดในประเทศไทย

Doctor of Philosophy (Health Sciences), 2023Introduction: Lung cancer is the most common cancer in males and the fourth most common in females. Although there are many novel effective treatments available on the market, patients are mainly unable to access them. The biggest barrier factor is the cost of treatment which may cause financial toxicity to the patients, family, or even to the healthcare system, especially in low or middle-income countries. This study aims to (1) evaluate the cost-effectiveness of applying immune checkpoint inhibitors (ICI) in second-line non-small cell lung cancer in Thailand., and (2) evaluate the financial toxicity among lung cancer patients in Thailand. Materials and Methods: Economics evaluation using clinical input from published clinical trials data together with the cost and utility information from face-to-face questionnaire interviews. The incremental cost-effectiveness of ICI compared with docetaxel was computed using partition survival and the Markov model. Financial toxicity evaluation using data from the questionnaires in the cross-sectional design. Results: The ICI treatment improved survival by 0.55 to 0.81 life years. The incremental cost of ICI treatment ranged from USD 18,683 for atezolizumab to USD 69,723 for pembrolizumab. The ICI treatment improves QALY of about 0.43-0.62. The ICER for nivolumab, pembrolizumab, and atezolizumab were USD 84,957, USD 115,365, and USD 30,003, respectively. About 66% of the patients with lung cancer experience catastrophic health expenditure (CHE) and 29% of the patients develop medical impoverishment. Conclusion: The ICI treatment provided better survival and QALY but was more costly. Atezolizumab was the most favored regimen compared with the other two ICI. However, the ICER for atezolizumab was higher than Thailand's cost-effectiveness acceptability threshold of USD 5,208. A significant proportion of lung cancer patients in Thailand experienced financial toxicity

Prevalence, associated factors, and clinical consequences of metabolic syndrome in chronic obstructive pulmonary disease patients: a 5-year prospective observational study

Background: Chronic obstructive pulmonary disease (COPD) is characterized by multiple systemic comorbidities, not only airflow limitation. Metabolic syndrome (MetS) is a common comorbidity. Patients with COPD have a higher risk of MetS than do healthy individuals. Objectives: We aimed to investigate the prevalence of and explore the factors associated with MetS in Thai COPD patients and to assess the clinical consequences of MetS after a 5-year follow-up period. Methods: A prospective observational study was conducted in patients with stable COPD at Songklanagarind Hospital between June 2015 and November 2019. MetS was defined according to the International Diabetes Federation 2005 criteria. The patients were followed-up for 5 years. The prevalence, associated factors, and consequences of MetS were analyzed. Results: A total of 115 patients with COPD were enrolled, of whom 95.3% were male. The overall prevalence of MetS was 37.4% (43 patients). Chronic bronchitis and high C-reactive protein (CRP) levels were independently and significantly associated with MetS in patients with COPD ( p  = 0.036 and 0.044, respectively). After following patients for 5 years, the incidence of cardiovascular disease and stroke, exacerbation rate, and mortality rate were significantly higher in the COPD with MetS group [relative risk (RR) = 15.36, 95% confidence interval (CI) = (2.13–110.67), RR = 45.43, 95% CI = (4.61–447.07), RR = 1.94, 95% CI = (1.40–2.70), and RR = 48.01, 95% CI = (1.12–2049.43), respectively]. Conclusion: The prevalence of MetS is high in patients with COPD. Chronic bronchitis and high CRP levels are associated with MetS in COPD. The incidence of clinical consequences was significantly higher in patients with COPD and MetS after a 5-year follow-up. Screening for MetS is strongly recommended for all patients with COPD

Serum miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer.

Tumor-promoting cytokines are a cause of tumor progression; therefore, identifying key regulatory microRNAs (miRNAs) for controlling their production is important. The aim of this study is to identify promising miRNAs associated with tumor-promoting cytokines in non-small cell lung cancer (NSCLC). We identified circulating miRNAs from 16 published miRNA profiles. The selected miRNAs were validated in the serum of 32 NSCLC patients and compared with 33 patients with other lung diseases and 23 healthy persons using quantitative real-time PCR. The cytokine concentration was investigated using the enzyme-linked immunoassay in the same sample set, with clinical validation of the miRNAs. The correlation between miRNA expression and cytokine concentration was evaluated by Spearman's rank correlation. For consistent direction, one up-regulated miRNA (miR-145) was found in four studies, and seven miRNAs were reported in three studies. One miRNA (miR-20a) and four miRNAs (miR-25-3p, miR-223, let-7f, and miR-20b) were reported in six and five studies. However, their expression was inconsistent. In the clinical validation, serum miR-145 was significantly down-regulated, whereas serum miR-20a was significantly up-regulated in NSCLC, compared with controls. Regarding serum cytokine, all cytokines [vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and transforming growth factor β (TGF-β)], except tumor necrosis factor-α (TNF-α), had a higher level in NSCLC patients than controls. In addition, we found a moderate correlation between the TGF-β concentration and miR-20a (r = -0.537, p = 0.002) and miR-223 (r = 0.428, p = 0.015) and a weak correlation between the VEGF concentration with miR-20a (r = 0.376, p = 0.037) and miR-223 (r = -0.355, p = 0.046). MiR-145 and miR-20a are potential biomarkers for NSCLC. In addition, the regulation of tumor-promoting cytokine, through miR-20a and miR-223, might be a new therapeutic approach for lung cancer

Afatinib as first-line treatment of older patients with EGFR mutation-positive non-small-cell lung cancer: Subgroup analyses of the LUX-Lung 3, LUX-Lung 6 and LUX-Lung 7 trials

Background Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Patients and Methods Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus cisplatin/pemetrexed (LUX-Lung 3 [LL3]) or cisplatin/gemcitabine (LUX-Lung 6 [LL6]), or versus gefitinib (250 mg/d; LUX-Lung 7 [LL7]). We report subgroup analyses according to age, including 65 years or older versus younger than 65 years (preplanned; LL3/LL6) and additional cutoffs up to 75 years and older (exploratory; LL7). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results Among the 134 of 345 (39%) and 86 of 364 (24%) patients aged 65 years and older in LL3 and LL6, median PFS was improved with afatinib versus chemotherapy (LL3: hazard ratio [HR], 0.64 [95% confidence interval (CI), 0.39-1.03]; LL6: HR, 0.16 [95% CI, 0.07-0.39]). Afatinib significantly improved OS versus chemotherapy in elderly patients with Del19+ NSCLC in LL3 (HR, 0.39 [95% CI, 0.19-0.80]). Among the 40 of 319 patients (13%) aged 75 years or older in LL7, median PFS (HR, 0.69 [95% CI, 0.33-1.44]) favored afatinib, consistent with the overall population. Afatinib-associated AEs in older patients were consistent with the overall populations. Conclusions Subgroup analyses of the LL3, LL6, and LL7 trials show that afatinib is an effective and tolerable treatment for patients with EGFRm+ NSCLC, independent of age

Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials

Background - Afatinib 40 mg/day is approved for first-line treatment of EGFR mutation-positive non-small-cell lung cancer (NSCLC). In the case of drug-related grade ≥3 or selected prolonged grade 2 adverse events (AEs), the dose can be reduced by 10 mg decrements to a minimum of 20 mg. Here, we evaluate the influence of afatinib dose reduction on AEs, pharmacokinetics and progression-free survival (PFS) in the phase III LUX-Lung 3 and 6 (LL3/6) trials. Patients and methods - Treatment-naïve patients with advanced EGFR mutation-positive NSCLC in LL3 (global) and LL6 (China, Thailand, South Korea) were randomized to afatinib or chemotherapy. All afatinib-treated patients (LL3, n = 229; LL6, n = 239) were included in the post hoc analyses. Incidence and severity of common AEs before and after afatinib dose reduction were assessed. Afatinib plasma concentrations were compared in patients who reduced to 30 mg versus those remaining at 40 mg. PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not. Results - Dose reductions occurred in 53.3% (122/229) and 28.0% (67/239) of patients in LL3 and LL6, respectively; most (86.1% and 82.1%) within the first 6 months of treatment. Dose reduction led to decreases in the incidence of drug-related AEs, and was more likely in patients with higher afatinib plasma concentrations. On day 43, patients who dose reduced to 30 mg (n = 59) had geometric mean afatinib plasma concentrations of 23.3 ng/ml, versus 22.8 ng/ml in patients who remained on 40 mg (n = 284). The median PFS was similar in patients who dose reduced during the first 6 months versus those who did not {LL3: 11.3 versus 11.0 months [hazard ratio (HR) 1.25]; LL6: 12.3 versus 11.0 months (HR 1.00)}. Conclusions - Tolerability-guided dose adjustment is an effective measure to reduce afatinib-related AEs without affecting therapeutic efficacy

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non-Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis

PURPOSE: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. MATERIALS AND METHODS: Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. RESULTS: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. CONCLUSION: Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.Y