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Background: Current clinical trial data on PARP inhibitors (PARPis)-related acute renal failure (ARF) are not entirely representative of real-world situations. Therefore, in this study, the US Food and Drug Administration Adverse Event Reporting System (FAERS) was used to evaluate PARPis-related ARF., Research Design and Methods: Data were obtained from 1 January 2015, to 30 September 2023. ARF event reports were analyzed based on four algorithms. The time-to-onset (TTO) and clinical outcomes of PARPis-associated ARF were assessed., Results: The total included cases were 2726. Significant signals were observed for olaparib, niraparib, and rucaparib (reporting odds ratio (ROR): 1.62, 95% confidence interval (CI): 1.49-1.78, 1.25, 95% CI: 1.19-1.32 and 1.59, 95% CI: 1.47-1.72 respectively). The median TTO of ARF onset was 57, 36, and 85 days for olaparib, niraparib, and rucaparib, respectively. The proportion of deaths with olaparib (9.88%) was significantly higher than for niraparib (2.52%) and rucaparib (2.94%) ( p  < 0.005). The proportion of life-threatening adverse events associated with niraparib (4.89%) was significantly higher than for rucaparib (0.98%) ( p  < 0.005)., Conclusions: ARF and PARPi were related, with the exception of talazoparib. More emphasis should be given to PARPis-related ARF due to the high proportion of serious AEs and delayed adverse reactions.

Background: Combining immune checkpoint and proton pump inhibitors is widely used in cancer treatment. However, the drug-drug interactions of these substances are currently unknown. This study aimed to explore drug-drug interactions associated with concomitant immune checkpoint and proton pump inhibitors., Methods: Data were obtained from the US Food and Drug Administration Adverse Event Reporting System from 2014 to 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratios (RORs) with 95% confidence intervals (95%Cls). The adjusted RORs (RORadj) were then analysed using logistic regression analysis, considering age, sex, and reporting year. Drug-drug interactions occur when a combination treatment enhances the frequency of an event. Further confirmation of the robustness of the findings was achieved using additive and multiplicative models, which are the two statistical methodologies for signal detection of DDIs using spontaneous reporting system., Results: The total number of reports on immune checkpoint combined with proton pump inhibitors was 4,276. Median patient age was 66 years (interquartile range [IQR]: 60-74 years). Significant interaction signals were observed for congenital, familial and genetic disorders (RORadj = 2.66, 95%CI, 1.38-5.14, additive models = 0.7322, multiplicative models = 3.5142), hepatobiliary disorders (RORcrude = 6.64, 95%CI, 5.82-7.58, RORadj = 7.10, 95%CI, 6.16-8.18, additive models = 2.0525, multiplicative models = 1.1622), metabolism and nutrition disorders (RORcrude = 3.27, 95%CI, 2.90-3.69, RORadj = 2.66, 95%CI, 2.30-3.08, additive models = 0.6194), and skin and subcutaneous tissue disorders (RORcrude = 1.41, 95%CI, 1.26-1.58, RORadj = 1.53, 95%CI, 1.34-1.75, additive models = 0.6927, multiplicative models = 5.3599). Subset data analysis showed that programmed death-1 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders; hepatobiliary disorders; and skin and subcutaneous tissue disorders. Programmed death ligand-1 combined with proton pump inhibitors was associated with adverse reactions of metabolism and nutrition disorders. Cytotoxic T-lymphocyte antigen-4 combined with proton pump inhibitors was associated with congenital, familial, and genetic disorders, and skin and subcutaneous tissue disorders., Conclusions: Based on real-world data, four Standardized MedDRA Query System Organ Class toxicities were identified as drug-drug interactions associated with combining immune checkpoint and proton pump inhibitors. Clinicians should be cautious when administering these drugs concomitantly. Preclinical trials and robust clinical studies are required to explore the mechanisms and relationships underlying interactions, thus improving understanding of drug-drug interactions associated with this combination therapy., (© 2024. The Author(s).)

Introduction: Multiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated., Objective: This study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs)., Methods: Disproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs)., Results: A total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan-Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab ( p < 0.001)., Conclusions: MM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Shan, Zhang, Liu, Xia and Wang.)

Antibody-drug conjugates (ADCs) are among the fastest-growing classes of anticancer drugs, making it crucial to evaluate their potential for causing peripheral neuropathy. We analyzed data from the FAERS database (January 1, 2014, to June 30, 2023) using disproportionality and Bayesian methods. We identified 3076 cases of ADC-associated peripheral neuropathy. Our study revealed significant signals for all ADCs (ROR 1.82, 95% CI 1.76-1.89). ADCs with tubulin-binding payloads showed significant peripheral neuropathy signals (ROR 2.31, 95% CI 2.23-2.40), whereas those with DNA-targeting (ROR 0.48, 95% CI 0.39-0.59) and topoisomerase 1 inhibitor (ROR 0.56, 95% CI 0.48-0.66) payloads exhibited non-significant signals. Signals for peripheral sensory neuropathy were 4.83, 2.44, 2.74, and 2.21 (calculated based on IC 025 ) for brentuximab vedotin, trastuzumab emtansine, enfortumab vedotin, and polatuzumab vedotin, while signals for peripheral motor neuropathy were 5.31, 0.34, 2.27, and 0.03, respectively. The median time to onset for all ADCs was 127 days (interquartile range 40-457). Tisotumab vedotin had the highest hospitalization rate at 26.67%, followed by brentuximab vedotin at 25.5%. Trastuzumab emtansine had the highest mortality rate ,with 80 deaths (11.96%) among 669 cases. Based on FAERS database, only ADCs with tubulin-binding payloads exhibited significant peripheral neuropathy signals. Brentuximab vedotin and enfortumab vedotin showed similar profiles for peripheral sensory neuropathy and motor neuropathy. Given the delayed time to onset and potentially poor outcomes, ADC-related peripheral neuropathy warrants significant attention., (© 2024. The Author(s).)

Introduction: Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date., Methods: The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC 025 ) > 0 or ROR (ROR 025 ) > 1 with at least 3 reports was considered statistically significant., Results: Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC 025 /ROR 025 for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC 025 for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of "fatal" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT., Conclusion: ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) have become increasingly available for multiple types of cancers, although the cardiovascular safety profiles of this combination therapy in real-world settings have not been elucidated to date. Therefore, we aimed to comprehensively investigate the cardiovascular toxicity profiles of ICIs combined with AGIs in comparison with ICIs alone., Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1 st quarter of 2014 to the 1 st quarter of 2022 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with ICIs alone, AGIs alone and combination therapy. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR 025 ) > 1 or IC (IC 025 ) > 0 with at least 3 reports was considered statistically significant., Results: A total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for combination therapy were extracted. Compared to the entire database of patients without AGIs or ICIs, cardiovascular AEs were overreported in patients with combination therapy (IC 025 /ROR 025 = 0.559/1.478), showing stronger signal strength than those taking ICIs alone (IC 025 /ROR 025 = 0.118/1.086) or AGIs alone (IC 025 /ROR 025 = 0.323/1.252). Importantly, compared with ICIs alone, combination therapy showed a decrease in signal strength for noninfectious myocarditis/pericarditis (IC 025 /ROR 025 = 1.142/2.216 vs . IC 025 /ROR 025 = 0.673/1.614), while an increase in signal value for embolic and thrombotic events (IC 025 /ROR 025 = 0.147/1.111 vs . IC 025 /ROR 025 = 0.591/1.519). For outcomes of cardiovascular AEs, the frequency of death and life-threatening AEs was lower for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis (37.7% vs . 49.2%) as well as in embolic and thrombotic events (29.9% vs . 39.6%). Analysis among indications of cancer showed similar findings., Conclusion: Overall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than ICIs alone, mainly due to an increase in embolic and thrombotic events while a decrease in noninfectious myocarditis/pericarditis. In addition, compared with ICIs alone, combination therapy presented a lower frequency of death and life-threatening in noninfectious myocarditis/pericarditis and embolic and thrombotic events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Cui, Deng, Wang and Ren.)