Severe cutaneous adverse reactions associated with immune checkpoint inhibitors therapy and anti-VEGF combination therapy: a real-world study of the FDA adverse event reporting system

ABSTRACTBackground Immune checkpoint inhibitors (ICIs) therapy combined with anti-vascular endothelial growth factor (anti-VEGF) regimens showed new hope for cancer patients and considered as future pillar of cancer therapy. However, severe cutaneous adverse reactions (SCARs) in patients with ICIs and anti-VEGF combined therapy raise a serious concern and remain thoroughly assessed in clinics.Research design and methods Data retrieved from the first quarter of 2004 to the third quarter of 2022 in FAERS database underwent disproportionality analysis and Bayesian analysis were utilized to detect and assess the SCAR signals of ICIs and ICIs and anti-VEGF combined therapy for comparison.Results In total, 854 (1.10%) and 80 (1.06%) reports on SCARs associated with ICIs and a combination of ICIs and anti-VEGF therapy, respectively, were analyzed. Most of SCARs reports were associated with the use of pembrolizumab (36.01%), nivolumab (23.97%) and a combination of ipilimumab and nivolumab (19.71%). A use of atezolizumab and bevacizumab combined therapy (60.00%) caused the most SCARs records out of ICIs and anti-VEGF combined therapies.Conclusions Treatment with joint therapy of ICIs and anti-VEGF agents may cause severe cutaneous adverse events. It is vital to identify ICI-related SCARs early, and to manage them appropriately.KEYWORDS: Immune checkpoint inhibitorsanti-VEGF agentspharmacovigilanceFAERSsevere cutaneous adverse reactions Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresOne reviewer has served on advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, has received research funding from BMS and Incyte, and has patents pending for use of MHC-II as a biomarker for immune checkpoint inhibitor response, and abatacept as treatment for immune-related adverse events. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.Author contribution statementThe study was conceived, designed, and co-written by C. L., Y. X., and A. L. The acquisition of data was performed by C. L., and Z. L. The draft was further analyzed and revised by Q. S. All authors contributed to the analyses of the data, discussed the results, edited the manuscript, and approved the final manuscript. Funding was obtained by C. L. All studies were supervised by A. L.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2251381Additional informationFundingThis paper is funded by National Natural Science Foundation of China and the grant number is [82003910].