{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:14:24Z","timestamp":1787166864154,"version":"build-2736575974"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Understanding approaches to managing treatment-related adverse events (AEs) in immunotherapy and tyrosine kinase inhibitor\u2013based treatments in a clinical setting is critical for reaching optimal patient outcomes.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the management of AEs in community practices during first-line axitinib plus pembrolizumab therapy for advanced renal cell carcinoma (aRCC).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This study comprised a cross-sectional electronic physician survey and a multisite, retrospective cohort study of the medical records of US patients with aRCC who initiated first-line axitinib-pembrolizumab between April 22, 2019, and January 31, 2024. Data were analyzed from September 18 to December 20, 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n First-line axitinib-pembrolizumab therapy.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Main outcomes included patient characteristics, treatment patterns, AEs, and physician perspectives on management of AEs. End points were summarized using descriptive statistics as well as the Kaplan Meier method for time-to-event outcomes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 300 patients with aRCC who received first-line axitinib-pembrolizumab therapy (mean [SD] age, 66.0 [9.3] years; 183 [61.0%] male) and 25 physicians (mean [SD] time in practice, 14.6 [7.3] years) were included. The median follow-up was 12.3 (IQR, 8.1-21.6) months. Most patients (285 [95.0%]) started treatment with axitinib at a dose of 5 mg twice daily. Overall, 43 patients (14.3%) required at least 1 dose reduction of axitinib, 41 (13.7%) required at least 1 interruption of axitinib, and 18 (6.0%) required at least 1 interruption of pembrolizumab. AEs were the most common reason for reductions and interruptions. For patients who discontinued axitinib (n = 141) and\/or pembrolizumab (n = 146), the most common reason was disease progression (111 of 141 [78.7%] for axitinib and 110 of 146 [75.3%] for pembrolizumab); 11 of 141 (7.8%) discontinued axitinib and 14 of 146 (9.6%) discontinued pembrolizumab due to AEs. All participating physicians were medical oncologists and 22 (88.0%) practiced in community settings. Sixteen physicians (64.0%) had access to multispecialty consultation for managing AEs. Nineteen physicians (76.0%) indicated that overall survival was the top factor in their selection of first-line axitinib-pembrolizumab therapy (6 [24.0%] selected safety profile as one of the top 3 factors). Patient comorbidities (16 of 21 [76.2%]) and performance status (15 of 21 [71.4%]) were important factors when considering treatment modification vs discontinuation.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study including patients with aRCC who received first-line axitinib-pembrolizumab therapy and physicians with experience treating aRCC, few patients permanently discontinued treatment due to AEs, and physicians reported balancing treatment effectiveness, safety, and patient-level factors when managing treatment-related AEs. Future work is warranted to evaluate the effects of AE management on clinical outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.14061","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:00:24Z","timestamp":1779375624000},"page":"e2614061","source":"Crossref","is-referenced-by-count":1,"title":["Axitinib-Pembrolizumab and Adverse Event Management in Patients With Advanced Renal Cell Carcinoma"],"prefix":"10.1001","volume":"9","author":[{"given":"Neil J.","family":"Shah","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaa","family":"Ababio","sequence":"additional","affiliation":[{"name":"Pfizer Inc, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Eccleston","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Surrey, United 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