Hypertension associated with niraparib in cancer patients: A pharmacovigilance analysis based on the FAERS database and meta-analysis of randomized controlled trials.

BACKGROUND: Niraparib plays a crucial role in the treatment of ovarian cancer. A comprehensive understanding of the incidence and risk of hypertension associated with niraparib would be of vital importance to healthcare practitioners. METHODS: In this study, an observational, retrospective, pharmacovigilance study was conducted based on the FDA Adverse Event Reporting System (FAERS) database. Cases of hypertension related to niraparib were extracted for disproportionality analysis from the first quarter (Q1) of 2017 to Q1 of 2023. Moreover, a separate meta-analysis was performed using the randomized controlled trials (RCTs) on niraparib for cancer treatment published in PubMed, Embase, and Web of Science from inception to May 31st, 2023. The primary outcomes were the incidence and risk of hypertension associated with niraparib. RESULTS: In the FAERS, 1196 hypertension cases were found to be related to niraparib treatment. Notably, niraparib exhibited the highest level of disproportionality, as indicated by a reporting odds ratio (ROR) of 2.85 (95% CI, 2.69-3.01), suggesting a greater likelihood of causing hypertension compared to other poly-ADP-ribose polymerase (PARP) inhibitors (P < 0.01). Our safety meta-analysis included five pivotal RCTs of niraparib that reported hypertension. In comparison to placebo treatment, the meta-analysis demonstrated a significant increase in the risk of hypertension with niraparib (OR 2.84 [95% CI, 2.17-3.72], P < 0.01), with no heterogeneity observed among the studies (I2 = 0%, χ2 = 2.02, P = 0.73). The incidence of niraparib-induced hypertension was determined to be 16.9% (95% CI, 14.9-18.9; I2 = 34%). CONCLUSIONS: These findings suggest that hypertension is a distinctive adverse event associated with niraparib compared to other PARP inhibitors. Niraparib significantly increases the risk of hypertension that needs early recognition and management in clinical medication.

Incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted antibody-drug conjugates: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs. METHODS: We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627). RESULTS: Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5-1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types. CONCLUSION: Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.

Knowledge, attitudes, and practices toward cancer pain management amongst healthcare workers (physicians, pharmacists, and nurses): a cross-sectional study from first-tier cities in China.

PURPOSE: China is currently one of the countries with the largest increased number of new cancer cases in the world, but cancer pain management (CPM) is still inadequate. This study uses a questionnaire to demonstrate the status and differences in knowledge, attitude and practice (KAP) of CPM among healthcare workers (HCWs) in developed regions of China, to find deficiencies and priorities for improvement, from which areas and advantages of the role of pharmacists and mobile devices can be explored. METHODS: This study used data from a questionnaire on CPM from March to June 2019. The study population consisted of a total of 515 HCWs in four first-tier developed cities in China. The questionnaire has four major components, analysis of differences in KAP of different occupations through one-way analysis of variance (ANOVA). RESULTS: Among the respondents, the physicians had the highest knowledge scores toward CPM, pharmacists had the lowest practice scores. Around half of the respondents indicated that their hospital or department have a pharmacist participating in CPM. Physicians and nurses were more likely to expect pharmacists to provide drug counseling. The HCWs interviewed most expect that the mobile-based pain management system can automatically screen and mark patients with pain. CONCLUSION: From this study, it can be suggested that pharmacists and nurses in the CPM team should actively promote relevant knowledge. Besides, pharmacists should focus on improving practical ability such as increasing the frequency of pain assessment. Multidisciplinary collaboration and the introduction of mobile devices can improve and refine the CPM.

Evaluation of pharmacist interventions as part of a multidisciplinary cancer pain management team in a Chinese academic medical center.

OBJECTIVE: The objective of this study was to evaluate pharmacist interventions in the cancer pain management of hospitalized patients, focusing on a clinically meaningful change in drug-related problems and pain score. METHODS: A retrospective data analysis was performed at a single academic comprehensive cancer center. Hospitalized patients with moderate to severe pain who had already received analgesic medication for at least 3 consecutive days were included. For patients who met the criteria for admission, a pharmacist followed up daily during hospitalization and evaluated the patient during pre- (first) and postintervention (second, third, and fourth) visits. Medication problems, medication changes, and changes in pain scores were assessed. RESULTS: A total of 195 patients were included in the study. The pharmacist identified 12 types of pharmacotherapeutic drug-related problems. The top 3 problems were nonadherence or missed doses (27.69%), inappropriate opioid selection (22.56%), and inappropriate dosage (16.41%). After the intervention of pharmacists, these drug-related problems decreased by 74.54% on average. Across all visits, the changes in pain scores (mean ± SD: 2.80 ± 1.92 vs. 1.90 ± 1.58, P < 0.05) and the number of patients with mild (172 vs. 128, P < 0.05), moderate (58 vs. 21, P < 0.05), and severe pain (9 vs. 2, P < 0.05) indicated a marked decrease in patients' pain levels after the inclusion of pharmacist in the cancer pain multidisciplinary management team (CPMMT). CONCLUSION: Participation by the pharmacist in the CPMMT led to a marked reduction in most of the drug-related problems and a statistically significant change in pain score during the 4 visits, indicating that pharmacists play an active role in CPMMT.

Opioid Nonadherence Risk Prediction of Patients with Cancer-Related Pain Based on Five Machine Learning Algorithms.

Objectives: Opioid nonadherence represents a significant barrier to cancer pain treatment efficacy. However, there is currently no effective prediction method for opioid adherence in patients with cancer pain. We aimed to develop and validate a machine learning (ML) model and evaluate its feasibility to predict opioid nonadherence in patients with cancer pain. Methods: This was a secondary analysis from a cross-sectional study that included 1195 patients from March 1, 2018, to October 31, 2019. Five ML algorithms, such as logistic regression (LR), random forest, eXtreme Gradient Boosting, multilayer perceptron, and support vector machine, were used to predict opioid nonadherence in patients with cancer pain using 43 demographic and clinical factors as predictors. The predictive effects of the models were compared by the area under the receiver operating characteristic curve (AUC_ROC), accuracy, precision, sensitivity, specificity, and F1 scores. The value of the best model for clinical application was assessed using decision curve analysis (DCA). Results: The best model obtained in this study, the LR model, had an AUC_ROC of 0.82, accuracy of 0.82, and specificity of 0.71. The DCA showed that clinical interventions for patients at high risk of opioid nonadherence based on the LR model can benefit patients. The strongest predictors for adherence were, in order of importance, beliefs about medicines questionnaire (BMQ)-harm, time since the start of opioid, and BMQ-necessity. Discussion. ML algorithms can be used as an effective means of predicting adherence to opioids in patients with cancer pain, which allows for proactive clinical intervention to optimize cancer pain management. This trial is registered with ChiCTR2000033576.

Genetic and Clinical Factors Associated with Opioid Response in Chinese Han Patients with Cancer Pain: An Exploratory Cross-Sectional Study.

INTRODUCTION: Studies have shown that genetic variation and environmental factors are associated with individual differences in therapeutic efficacy and side effects of opioids. However, the focus of these studies has been on a single factor of single-nucleotide polymorphisms (SNPs) or haplotypes, for which results have rarely been validated. For complex traits, such as cancer pain and opioid response, interactions between multiple genetic variation and environmental factors need to be considered to explain the opioid individual differences. METHODS: We conducted an exploratory two-stage cross-sectional study with 1027 Chinese patients who were taking strong opioid medications for their cancer pain, and genotyped 110 SNPs to explore the association of SNPs, haplotypes, gene-gene and gene-environment interactions with opioid dose, pain relief, and opioid-induced constipation. RESULTS: Due to the failure to meet Benjamini-Hochberg criteria in the discovery stage or to be validated in replication stage, no association was found between SNPs, haplotypes, paired SNP-SNP interactions or multi-dimensional gene-gene interactions and opioid response. However, for gene-environment interactions, optimal models have been constructed in all phenotypes of opioid response. CONCLUSIONS: This study reveals for the first time that construction of multidimensional gene-environment interactions enables better interpretations of the effect of genetic variation and environmental factors on the opioid response in patients with cancer pain. TRIAL REGISTRATION: Chictr.org.cn, identifier, ChiCTR2000033576.

Efficacy and Safety of Thalidomide As a Pre-Medication of Chemotherapy-Induced Nausea and Vomiting (CINV) Following Highly Emetogenic Chemotherapy (HEC): A Systematic Review and Meta-Analysis.

BACKGROUND: In China, thalidomide (THD) has been used to prevent chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC); however, there is limited evidence on the efficacy and safety of THD in this setting. The aim of this study was to evaluate the efficacy, safety, and impact on quality of life (QoL) of THD on CINV following HEC. METHODS: Electronic databases were systematically searched for all randomized controlled trials (RCTs) in HEC using THD. The primary outcomes were complete response (CR) and no nausea, Secondary outcomes were the incidence of adverse events and QoL related indicators. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a fixed-effects model. In the case of heterogeneity (I2≥50%), a random-effects model was performed. RESULTS: A total of 3168 patients were included from 34 RCTs. In terms of CR rate, THD plus 5-HT3 receptor antagonist (5-HT3RA) with or without dexamethasone (DEX) was significantly higher than 5-HT3RA with or without DEX in the acute phase (74.4% vs 67.4%; RR 1.10), delayed phase (70.6% vs 50.4%; RR 1.53), and overall phase (68.4% vs 53.4%; RR 1.28). In terms of no nausea rate, the THD group was also significantly higher than the control group in the acute phase (61.7% vs 55.5%; RR 1.12), delayed phase (50.5% vs 30.0%; RR 1.69), and overall phase (44.6% vs 29.9%; RR 1.50). There was no statistical difference in the incidence of fatigue, headache, diarrhea, rash, hepatorenal damage, and myelosuppression between those with and without THD. The incidence of increase in KPS scores, weight gain, appetite improvement, and sleep quality improvement were significantly higher with the addition of THD. CONCLUSIONS: THD may be effective and safe for the prevention of CINV patients treated with HEC and may improve QoL.

Practice, Knowledge, and Attitude of Health Care Providers regarding Cancer Pain Management: A National Survey.

Background: A lack of knowledge and inadequate practices of health care providers (HCPs) are the main obstacles to effective cancer pain management (CPM). The main objective of the study was to evaluate the CPM knowledge, CPM practice, and attitudes towards pharmacists' participation and advanced methods in CPM of physicians, nurses, and pharmacists in China. Methods: An open online survey was adopted using social media software (WeChat) as the platform to conduct a nationwide survey of HCPs involved in CPM in public medical institutions at all levels in China from March to June 2019. Results: A total of 1279 physicians, 2267 nurses, and 1466 pharmacists participated in the survey. Among the three types of professionals, nurses had the highest level of practical ability (61.63 ± 28.99) and best attitudes towards pharmacists' participation and advanced methods in CPM (72.05 ± 33.71) and physicians had the best mastery of CPM-related knowledge (69.60 ± 28.45), while pharmacists performed the worst in these three aspects (50.04 ± 26.69, 61.49 ± 28.95, and 62.07 ± 36.46, respectively). Only 19.69% of the hospitals had a pharmacist to tumor patient ratio ≥1 : 50. Hierarchical analysis showed that passing a good pain management (GPM) ward program and participating in advanced training had positive impacts on the scores of all three parts in the three professions (ptrend <0.05). Conclusions: HCPs' levels of practice, knowledge, and attitudes towards pharmacists and advanced methods of CPM were average in China; however, pharmacists had the worst performance, which demonstrates a need for further improvement. Furthermore, GPM ward programs and advanced trainings are helpful for improving CPM levels.