| アブストラクト | Background: Sotorasib, a KRAS G12C inhibitor, is approved for treating non-small cell lung cancer (NSCLC) and has shown a distinct safety profile in randomized clinical trials (RCTs). However, post-marketing pharmacovigilance is crucial to identify real-world safety signals including sex-specific differences that may not be evident in controlled trial settings. Methods: This analysis reviewed 845 individual case safety reports (ICSRs) from the EudraVigilance (EV) database between 1 January 2021, and 8 April 2025, involving NSCLC patients treated with sotorasib. Adverse drug reactions (ADRs) were assessed by sex, seriousness, outcome, and system organ class (SOC). Disproportionality analyses were conducted to detect sex-specific safety signals, and results were compared with data from the CodeBreaK200 RCT by using a two-proportion z-test. Results: Among the ICSRs, 49.2% involved male and 40.1% female patients. Serious ADRs accounted for 47.5% of cases, with females at higher risk (relative risk [RR] = 1.31; 95% confidence interval (CI): 1.22-1.40; p < 0.0001). The most frequently reported SOCs were neoplasms (15.8%), gastrointestinal disorders (15.3%), and hepatobiliary disorders (11.5%). Four sex-specific safety signals were identified: women had a significantly increased risk of cholestasis (RR = 3.37) and hepatotoxicity (RR = 3.01), while men were less likely to report decreased appetite (RR = 0.20) and rash (RR = 0.14). Real-world data showed lower reporting of diarrhea, fatigue, nausea, and liver enzyme elevations (p < 0.0001). Conclusions: Real-world pharmacovigilance supports the RCT findings and highlights sex-specific risks, thus emphasizing the importance of sex-aware monitoring and personalized toxicity management. |
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| ジャーナル名 | Pharmaceuticals (Basel, Switzerland) |
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| Pubmed追加日 | 2025/10/29 |
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| 投稿者 | Speranza, Desiree; Marafioti, Mariapia; Musarra, Martina; Cianci, Vincenzo; Omero, Fausto; Spagnolo, Calogera Claudia; Calabro, Marco; Silvestris, Nicola; Irrera, Natasha; Santarpia, Mariacarmela |
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| 組織名 | Department of Chemical, Biological, Pharmaceutical and Environmental Sciences,;University of Messina, 98166 Messina, Italy.;Department of Clinical and Experimental Medicine, University of Messina, 98122;Messina, Italy.;Medical Oncology Unit, Department of Human Pathology "G.Barresi", University of;Messina, 98125 Messina, Italy.;Department of Biomedical and Dental Sciences and Morphofunctional Imaging,;University of Messina, 98125 Messina, Italy.;Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari,;Italy. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41155693/ |
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