Immune-related adverse-event signals of durvalumab: cross-database pharmacovigilance analysis of WHO-VigiAccess and FAERS with comparative assessment versus atezolizumab

Immune-related adverse-event signals of durvalumab: cross-database pharmacovigilance analysis of WHO-VigiAccess and FAERS with comparative assessment versus atezolizumab | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Immune-related adverse-event signals of durvalumab: cross-database pharmacovigilance analysis of WHO-VigiAccess and FAERS with comparative assessment versus atezolizumab Furong Sun, Qinwei Wu, Jing Li, Shouzhen Liu, Jie Hua, Yuzhu Gao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9154831/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Durvalumab has become a key programmed death-ligand 1 (PDL1) inhibitor in modern oncology, particularly in thoracic malignancies. As its clinical use expands, immune-related adverse events (irAEs) have emerged as a major safety concern. However, comprehensive real-world characterization of durvalumab-associated irAEs and direct comparison with other PD-L1 inhibitors remain limited. This study aimed to characterize the immune toxicity profile of durvalumab using multi-database pharmacovigilance data and to compare its reporting patterns with those of atezolizumab. Methods: A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) and the WHO VigiAccess database. FAERS reports from 2017Q2 to 2025Q4 were analyzed after deduplication and restriction to neoplasm-related indications. Signal detection for predefined irAEs was performed using four disproportionality algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker 1 (MGPS). Head-to-head comparisons between durvalumab and atezolizumab were performed using multivariable logistic regression with adjustment for demographic and reporting factors. VigiAccess data were used for cross-database descriptive corroboration. Results: A total of 9,357 durvalumab-associated reports and 21,247 atezolizumab-associated reports were included in the FAERS analysis. All predefined core irAE domains met the primary signal threshold for durvalumab, with pulmonary events contributing the largest reporting burden and showing the strongest disproportionality. Selected preferred-term core signals were concentrated in cardiac, dermatologic, endocrine, and gastrointestinal phenotypes, with immune-mediated myocarditis showing the most pronounced retained PT-level signal. In the adjusted lung cancer-restricted head-to-head analysis, durvalumab showed higher reporting odds for pulmonary irAEs than atezolizumab (aOR 1.63, 95% CI 1.44–1.85) but lower reporting odds for renal, hepatobiliary, neurologic, hematologic, gastrointestinal, and dermatologic irAEs. Median time-to-onset for major irAE domains ranged from 34 to 56 days, and the broad organ-level reporting pattern was generally consistent with WHO VigiAccess. Conclusion: Durvalumab demonstrates a broad immune-related adverse-event profile with a distinct pulmonary predominance in real-world reporting. Compared with atezolizumab, the main relative excess signal was pulmonary toxicity, whereas several non-pulmonary domains were reported less frequently. These findings support early pulmonary-focused monitoring while maintaining vigilance for rare high-severity cardiac events and clinically important renal, hepatobiliary, endocrine, gastrointestinal, and dermatologic toxicities. Durvalumab immune-related adverse events pharmacovigilance FAERS VigiAccess atezolizumab Full Text Additional Declarations No competing interests reported. Supplementary Files Table1baselineprimarylungcohort.tex Table2domainsignalmain.tex Table3selectedptsignalmain.tex Table4h2hdomainprimarylung.tex Table5ttoseriousoutcomes.tex FigureS1yeartrend300dpi.png FigureS3h2hdomainallneoplasm300dpi.png FigureS2thoraciccontextptsignal300dpi.png FigureS4sensitivityforest300dpi.png Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 15 Apr, 2026 Editor invited by journal 19 Mar, 2026 Editor assigned by journal 19 Mar, 2026 Submission checks completed at journal 19 Mar, 2026 First submitted to journal 18 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9154831","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625053915,"identity":"ed36b84c-1d88-4f8a-9ace-243be4253e02","order_by":0,"name":"Furong Sun","email":"","orcid":"","institution":"Zhoushan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Furong","middleName":"","lastName":"Sun","suffix":""},{"id":625053917,"identity":"9530f775-5870-4ea7-9631-df7bbf090676","order_by":1,"name":"Qinwei Wu","email":"","orcid":"","institution":"Guangzhou 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atezolizumab\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC 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As its clinical use expands, immune-related adverse events (irAEs) have emerged as a major safety concern. However, comprehensive real-world characterization of durvalumab-associated irAEs and direct comparison with other PD-L1 inhibitors remain limited. This study aimed to characterize the immune toxicity profile of durvalumab using multi-database pharmacovigilance data and to compare its reporting patterns with those of atezolizumab.\u003c/p\u003e\n\u003cp\u003eMethods: A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) and the WHO VigiAccess database. FAERS reports from 2017Q2 to 2025Q4 were analyzed after deduplication and restriction to neoplasm-related indications. Signal detection for predefined irAEs was performed using four disproportionality algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker 1 (MGPS). Head-to-head comparisons between durvalumab and atezolizumab were performed using multivariable logistic regression with adjustment for demographic and reporting factors. VigiAccess data were used for cross-database descriptive corroboration.\u003c/p\u003e\n\u003cp\u003eResults: A total of 9,357 durvalumab-associated reports and 21,247 atezolizumab-associated reports were included in the FAERS analysis. All predefined core irAE domains met the primary signal threshold for durvalumab, with pulmonary events contributing the largest reporting burden and showing the strongest disproportionality. Selected preferred-term core signals were concentrated in cardiac, dermatologic, endocrine, and gastrointestinal phenotypes, with immune-mediated myocarditis showing the most pronounced retained PT-level signal. In the adjusted lung cancer-restricted head-to-head analysis, durvalumab showed higher reporting odds for pulmonary irAEs than atezolizumab (aOR 1.63, 95% CI 1.44–1.85) but lower reporting odds for renal, hepatobiliary, neurologic, hematologic, gastrointestinal, and dermatologic irAEs. Median time-to-onset for major irAE domains ranged from 34 to 56 days, and the broad organ-level reporting pattern was generally consistent with WHO VigiAccess.\u003c/p\u003e\n\u003cp\u003eConclusion: Durvalumab demonstrates a broad immune-related adverse-event profile with a distinct pulmonary predominance in real-world reporting. Compared with atezolizumab, the main relative excess signal was pulmonary toxicity, whereas several non-pulmonary domains were reported less frequently. These findings support early pulmonary-focused monitoring while maintaining vigilance for rare high-severity cardiac events and clinically important renal, hepatobiliary, endocrine, gastrointestinal, and dermatologic toxicities.\u003c/p\u003e","manuscriptTitle":"Immune-related adverse-event signals of durvalumab: cross-database pharmacovigilance analysis of WHO-VigiAccess and FAERS with comparative assessment versus atezolizumab","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 10:34:46","doi":"10.21203/rs.3.rs-9154831/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-04-15T06:56:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-19T11:52:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-19T11:29:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-19T11:28:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-03-18T05:09:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"daba9227-d6e2-40c8-a308-67770dd35daa","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T10:34:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 10:34:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9154831","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9154831","identity":"rs-9154831","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}