Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Sorbara, Emanuela Elisa; Russo, Giulia; Cicala, Giuseppe; Franchina, Tindara; Santarpía, Mariacarmela; Silvestris, Nicola; Spina, Edoardo

doi:10.3390/cancers15061851

Cited by 7 publications

(4 citation statements)

References 61 publications

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“…Moreover, compared to the previous studies, incidence of hand-foot syndrome was lower in the current study (21% in phase III study and 43.7% in a phase I study). Post-marketing data also showed a high probability of ripretinib to report skin and subcutaneous tissue disorders, especially for alopecia (odds ratio: 1.5; 95% CI 1.0–2.2) [ 21 ]. In the INVICTUS trial, patients were stratified by the known prognostic variables such as ECOG PS and the number of previous therapies [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…The most common AEs reported were alopecia (49–63% in women), myalgia (28%), nausea (26%), fatigue (26%), hand-foot syndrome (21%), and diarrhea (20%) [ 20 ]. Furthermore, the analysis of European individual case safety reports showed a lower reporting probability of AEs with ripretinib than other TKIs, indicating a good safety profile of ripretinib [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Large-Scale, Multicenter, Prospective Registry Study of Ripretinib in Advanced GIST: A Real-World Study from China

Zhang,

Qiu

et al. 2023

Adv Ther

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Introduction Tyrosine-kinase inhibitors (TKIs) have become the standard treatment for patients with advanced gastrointestinal stromal tumor (GIST); however, secondary mutations can still drive disease progression. Studies have shown that ripretinib, a novel switch-control TKI, inhibits various primary and secondary drug-resistant mutations. There is a paucity of data on the effectiveness and safety of ripretinib in a real-world setting. This prospective, large-scale, real-world registry study aimed to evaluate the effectiveness and safety of ripretinib as a fourth-line treatment in Chinese patients with advanced GIST. Methods Patients ≥ 18 years of age having recurrent/metastatic GIST were enrolled. Key endpoints were median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) incidence. Univariate and multivariate analyses were conducted to identify various parameters associated with PFS. Results A total of 240 patients were enrolled. After a median follow-up period of 6.5 months, the mPFS [95% confidence interval (CI)] was 7.70 (6.60, 8.60) months and the mOS was not reached. Multivariate analysis revealed association of Eastern Cooperative Oncology Group (ECOG) performance status score with PFS and superior benefits for non-gastric was observed as compared to gastric GISTs [hazard ratio (HR) 0.58, 95% CI (0.39–0.86)]. Disease control rate and tumor shrinkage (any magnitude) was 73% and 43%, respectively. Ripretinib was also effective in the subgroup of patients with different gene mutations. The toxicities were tolerable, and most reported AEs were alopecia (17.1%) and hand-foot syndrome (15.4%). Conclusion Ripretinib demonstrated effectiveness and a tolerable safety profile, making it a viable option as a fourth- or later-line treatment in Chinese patients with advanced GISTs, especially for non-gastric GISTs. Trial Registration ClinicalTrials.gov identifier, NCT05697107. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02576-0.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Large-Scale, Multicenter, Prospective Registry Study of Ripretinib in Advanced GIST: A Real-World Study from China

Zhang,

Qiu

et al. 2023

Adv Ther

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“…The strength of this study lies in the large number of reports analyzed, which contribute to the cumulative knowledge of the nephrotoxicity of oral TKIs in mCRC. The use of a global database and the combination of a disproportionality approach with case/non-case evaluation has been documented in the literature [ 23 , 51 ]. One of the main advantages of using the SRS database is its ability to generate new potential safety signals for ADRs that may remain undetected during the pre-marketing phase [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database

Russo,

Barbieri,

Sorbara

et al. 2023

Biomedicines

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Background: this study assessed the nephrotoxicity of regorafenib (REG) and encorafenib (ENC) in metastatic colorectal cancer (mCRC) through an analysis of reports from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) database. Methods: descriptive and disproportional analyses were performed for all reports using ENC and REG as the primary suspect. Results: A total of 379 reports had at least one renal adverse drug reaction (ADR), and these ADRs were mainly related to REG (93.1%). Potential safety signals for REG included chromaturia (n = 44; ROR = 12.00, CI 95% = 8.92–16.16; IC = 2.36, IC025–IC075 = 2.06–2.66), hydronephrosis (10; 8.70, 4.67–16.19; 1.85, 1.23–2.47), nephrotic syndrome (7; 5.73, 2.73–12.03; 1.47, 0.73–2.21), renal impairment (53; 4.16, 3.17–5.45; 1.39, 1.12–1.66), dysuria (19; 3.06, 1.95–4.81; 1.06, 0.61–1.52), renal failure (38; 1.66, 1.20–2.28; 0.49, 0.17–0.81), and acute kidney injury (AKI) (43; 1.46, 1.08–1.97; 0.37, 0.07–0.67). For ENC, consistent disproportionalities were observed for AKI (n = 11; ROR = 3.79, CI 95% = 2.09–6.90; IC = 1.32, IC025–IC075 = 0.72–1.91) and dysuria (4; 6.50, 2.43–17.39; 1.86, 0.88–2.85). Conclusions: these findings highlight some not extensively reported renal ADRs that require further investigations to better characterize the safety profiles of REG and ENC in patients with mCRC.

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“…It is make sure that, the distribution of ADRs over the years has been certainly influenced by the different timing of approval and the clinical use of TKIs ( Barbieri et al, 2023 ). In this study, the main indication of the MKIs are renal cacer and liver cancer (38.3% and 36.4%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Psychiatric adverse reactions to non-selective RET multi-kinase inhibitors: a large-scale pharmacovigilance analysis

et al. 2023

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Objective: The development of non-selective multi-kinase inhibitors (MKIs) has improved the. survival outcomes of patients with cancers. Psychiatric disorders represent an MKIs related AE of particular concern, as they are often ignored and may harm the patient’s personal and social functioning. Therefore, we use the public database to describe and evaluate psychiatric adverse events related to various non-selective RET MKIs. Provide evidence for optimizing drug administration in the clinic.Methods: We analyzed spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System FDA Adverse Event Reporting System in an observational and retrospective manner. Selecting psychiatric AEs to non-selective RET multikinase inhibitors (sorafenib, lenvatinib, vandetanib, cabozantinib, and sunitinib). We used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms to analyze suspected adverse reactions of psychiatric related induced by non-selective RET MKIs between January 2004 and September 2022.Results: As of September 2022, 1,108 non-selective RET MKIs ICSRs were related to psychiatric AEs. 706 were ADR ICSRs, and 402 were non-ADR ICSRs. There were more ADR cases in males (69.5%), and 71.8% of the cases were submitted from North America. The age group most frequently affected by psychiatric ADRs was individuals aged 50–64 years for sorafenib, whereas 65–74 years for sunitinib, cabozantinib, and lenvatinib. In all psychiatric ADRs ICSRs, excluding missing data (n = 329), the most common adverse outcome was hospitalization (260/377, 69.0%), and the most serious was death (100/377, 26.5%). What calls for special attention is that the percentage of death rate for sunitinib was highest (24/54, 44.4%) in sunitinib-related psychiatric ADRs ICSRs, (excluding missing data, n = 44), followed by lenvatinib (4/14, 28.6%). Based on ROR, PRR, BCPNN, and MGPS methods, sorafenib, sunitinib, cabozantinib, and lenvatinib are significantly associated with all ADRs, the strongest association was the association between cabozantinib and feeding disorder.Conclusion: Despite the limitations, our study found that, except for vandetanib, other four drugs have been reported to have significant psychiatric side effects. Clinicians need to recognize and monitor these potentially fatal adverse events. If it is suitable for treatment with vandetanib, doctors should choose vandetanib for treatment.

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Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Cited by 7 publications

References 61 publications

Large-Scale, Multicenter, Prospective Registry Study of Ripretinib in Advanced GIST: A Real-World Study from China

Large-Scale, Multicenter, Prospective Registry Study of Ripretinib in Advanced GIST: A Real-World Study from China

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database

Psychiatric adverse reactions to non-selective RET multi-kinase inhibitors: a large-scale pharmacovigilance analysis

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