A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Risk comparison of beta-lactam-induced anaphylaxis: Therapeutic stratification analysis in a Vietnamese pharmacovigilance database.

WHAT IS KNOWN AND OBJECTIVE: There is limited data on the specific risks of anaphylaxis induced by beta-lactam drugs. The aim of this study was to compare the risks of reporting beta-lactam-induced anaphylaxis using the national pharmacovigilance database of Vietnam (NPDV). METHODS: The multivariate generalised linear regression model was applied for signal generation and comparison of beta-lactams. RESULTS: Between 2010 and 2016, there were 2,921 reports of anaphylaxis (19.93%) from 14,655 spontaneous reports of beta-lactam use in the NDPV. Anaphylaxis signal generation was also found for the subgroup J01D (cephalosporins and carbapenems) (ROR = 1.27 [1.16-1.39]) and beta-lactamase-sensitive penicillins (ROR = 1.74 [1.27-2.35]). In the third generation cephalosporin subgroup, different risks were identified for the following combinations of beta-lactams: 1) cefotaxime with cefoperazone+sulbactam; 2) cefixime/cefpodoxime/cefdinir with cefoperazone+sulbactam or ceftizoxime/cefoperazone/ceftazidime/ceftriaxone/cefotaxime. For the second generation cephalosporin subgroup, different risks were found for cefotiam compared to cefmetazole, cefaclor, cefamandole and cefuroxime. WHAT IS NEW AND CONCLUSION: These findings identified and highlighted the different anaphylactic risks caused by various beta-lactams in the main subgroups.

Risk factors of Pancreatic Cancer in Vietnam: A Matched Case-Control Hospital-Based Study.

BACKGROUND: Data about the risk factors and pancreatic cancer in developing countries remain limited. We investigated for the first time the role of a number of risk factors (family cancer history, smoking, alcohol consumption, diabetes, inflammation disease, HBV infection) associated with pancreatic cancer among Vietnamese patients. METHODS: We included all patients hospitalized at 4 Northern Vietnamese hospitals (Vietnam National Cancer Hospital, Bach Mai, Viet Duc, Thai Nguyen) and diagnosed with pancreatic cancer during the period from 2017 to 2019. Risk factors of eligible patients were collected and assessed the associations using a matched control study and logistic regression model analysis. RESULTS: We identified 196 patients with diagnosis of pancreatic cancer of which 114 males and 82 females. The average age of the patient at the time of diagnosis was 58.28 years (standard deviation of 12.94, ranging from 25 to 87). Most of patients were diagnosed at advanced stage (85%). Smoking, diabetes, inflammation disease significantly increased the cancer risks (OR and 95% CI were 2.42 (1.38-4.37), 3.09 (1.54-6.68), 2.21 (1.42-3.45), respectively). HBV infection demonstrated a significant link with pancreatic cancer in univariate model (OR = 2.94 (1.08-9.36)), but not in multivariate model. However, cancer family history and alcohol drinkers did not show any significantly increased risk related to pancreatic cancer. CONCLUSIONS: Our finding showed smoking, diabetes, inflammation disease significantly increased the risk of pancreatic cancer in Vietnam.

Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in vietnamese spontaneous adverse drug reaction database: A subgroup approach to disproportionality analysis.

WHAT IS KNOWN AND OBJECTIVE: Despite the numerous studies investigating drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the understanding and quantitative data in developing countries remain limited. The study aimed to describe and quantify the drug-related risk of SJS/TEN in a resource-limited context using the Vietnamese spontaneous reporting database (VSRD) of adverse drug reactions. METHODS: Spontaneous reports relating to medium- and late-onset severe cutaneous adverse reactions (MLOSCAR) and SJS/TEN recorded in the VSRD from 2010 to 2015 were retrospectively analysed. The demographic characteristics and drug information were described and compared between SJS/TEN and other MLOSCAR reports. The drug-induced SJS/TEN signals were estimated using subgrouped disproportionality analysis with calculation of the reporting odds ratio (ROR) and the respective 95% confidence interval (CI). RESULTS: The VSRD received 2,849 MLOSCAR reports, 136 of which focus on SJS/TEN over a 6-year period. About 60% of SJS/TEN patients were male, and the majority of them were adults (mean age 42.5 ± 22.9). Up to 91.8% of drugs induced SJS/TEN within 1-28 days, and 45% SJS/TEN cases were evaluated as life-threatening. Positive signals were generated with carbamazepine (n = 25, ROR [95% CI] = 11.99 [7.07-19.92]), allopurinol (n = 15, ROR [95% CI] = 4.2 [2.20-7.59]), traditional/herbal medicines (n = 7, ROR [95% CI] = 2.76 [1.12-5.86]), colchicine (n = 4, ROR [95% CI] = 6.22 [1.69-18.72]), valproic acid (n = 3, ROR [95% CI] = 8.71 [1.89-30.19]) and meloxicam (n = 3, ROR [95% CI] = 7.09 [1.55-24.29]), which are well known for SJS/TEN. Cefixime (n = 5, ROR [95% CI] = 3.34 [1.13-8.00]) and paracetamol (n = 22, ROR [95% CI] = 5.23 [3.10-8.49]) also generated positive signals despite their popularity in Vietnam. WHAT IS NEW AND CONCLUSION: This first Vietnamese population-based study has highlighted original characteristics and signals of drug-induced SJS/TEN, which are relatively consistent with other worldwide data and typical for a developing country.

Drug-Induced Anaphylaxis in a Vietnamese Pharmacovigilance Database: Trends and Specific Signals from a Disproportionality Analysis.

INTRODUCTION: Despite the numerous studies investigating drug-induced anaphylaxis (DIA), understanding and quantitative data analysis in developing countries remain limited. The aim of our study is to describe and quantify DIA using the National Pharmacovigilance Database of Vietnam (NPDV). METHODS: Spontaneous reporting of adverse drug reactions (ADRs) recorded between 2010 and 2016 were retrospectively analysed to identify DIA reports. The trend and characteristics of DIA cases were described. Multivariate disproportionality analysis was used for signal generation. RESULTS: Overall, 4873 DIA cases (13.2% of total ADRs) were recorded in the NPDV, 111 of which resulted in death (82% of total ADR-induced deaths) over a 7-year period. There was a remarkable increase in DIA reporting over time (p < 0.001). The incidence rates of DIA reporting per total ADRs and per 100,000 inhabitants remained high (mean rates [95% CI] of 12.06 [9.88-14.24] and 0.77 [0.33-1.20], respectively). Concerning suspected drugs, systemic antibiotics (n = 3318, 68%) were mostly reported with a reporting odds ratio (ROR) and 95% CI of 2.35 [2.20-2.51]. In the case of antibiotic-induced anaphylaxis, the third-generation cephalosporins were predominant (n = 1961, 40.2%, ROR 2.39 [2.24-2.55]). We also noted drugs generally associated with DIA such as contrast agents (ROR 2.43 [2.04-2.88]) and anaesthetics (ROR 4.02 [3.30-4.89]). Furthermore, unexpected signals were observed for alpha-chymotrypsin (ROR 1.75 [1.23-2.44]) and amoxicillin/sulbactam (ROR 1.59 [1.18-2.10]), uncommonly reported in western countries. CONCLUSION: In recent years, cases of drug-induced DIA have increased in Vietnam, mostly due to antibiotics and third-generation cephalosporins. The inappropriate use of these drugs should be taken into account. Our findings also highlighted typical Vietnamese signals for alpha-chymotrypsin- and amoxicillin/sulbactam-induced anaphylaxis, which may relate to a specific sociological context in resource-limited countries.

Drug-induced bone loss: a major safety concern in Europe.

INTRODUCTION: Drug-induced bone loss remains the major cause of vertebral and hip fractures and significantly associated to morbidity and mortality. This article will review the common drugs identified as the causes of bone loss and the risk factors and management in European countries. AREAS COVERED: Beyond glucorticoid - the most cause of osteoporosis, many different drugs could cause harmful skeletal disorders. The antiepileptics, hormonal therapy, GnRH antagonists, aromatase inhibitors are well-known cause of bone loss. Osteoporosis and fractures risk also increased with calcineurin inhibitors, antiretroviral drugs, selective inhibitors of serotonin reuptake, loop diuretics, heparins, oral anticoagulants, high doses of thyroxine and proton pump inhibitors. EXPERT OPINION: Drugs are an important secondary cause of osteoporosis. Healthcare professionals should reassess the requirement for drugs and use the lowest dosage and shortest duration. Lifestyle changes, adequate calcium, vitamin D supplement, appropriate monitoring of bone status and initiating osteoporosis treatment if indicated are recommended when drugs having potential deleterious effects on bone are used, particularly in high risk patients. The update and further studies would provide concluded evidences of controversial drugs induced bone loss and determine the best prevention and treatment strategies.

Overview of Pharmacovigilance System in Vietnam: Lessons Learned in a Resource-Restricted Country.

Drug safety issues in developing countries are complex and sensitive, and health authorities cannot always simply implement decisions from developed countries because the health system, disease patterns, and lists of marketed drugs all differ. A system for proactive and effective surveillance of drugs in each nation is needed to identify and manage the exact drug-related problems faced by patients in these countries. Vietnam launched its university-based National Drug Information and Adverse Drug Reaction Monitoring Centre (NDIADRMC) in 2009, a significant step towards catching up with international trends. Although the center is still in its infancy and has limited resources, it has attained some achievements and largely met the minimum World Health Organization requirements for a functional pharmacovigilance center. The number of reports has increased rapidly, with some important signals generated from the national database leading to regulatory actions at a national level. In addition, this system can help detect drug-quality problems that are less common in developed countries. The success of the quantity and quality of reporting, risk assessment, and communication is still limited compared with more developed systems. A number of opportunities remain to enhance the system, particularly in risk communication and evaluation of the impact of pharmacovigilance, and to apply reporting outcomes to reduce drug-related risks throughout the country. More internal and external support is needed to develop a stronger and more comprehensive pharmacovigilance system.