{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:07:38Z","timestamp":1780070858177,"version":"3.54.0"},"reference-count":19,"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 Proprotein convertase subtilisin\/kexin type 9 (PCSK9) inhibition enhances antitumor efficacy of immune checkpoint inhibitors (ICIs) in preclinical models, but clinical evidence remains limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare survival and selected clinical outcomes among adults receiving ICIs for cancer who were treated with a PCSK9 inhibitor (PCSK9I) compared with high-intensity statin therapy.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This comparative effectiveness study used deidentified data from the TriNetX research network. Adults with non\u2013small cell lung cancer, melanoma, or renal cell carcinoma who received a programmed cell death 1 or a programmed cell death ligand 1 inhibitor between January 1, 2016, and December 31, 2024, were included. Follow-up began from ICI treatment initiation through January 13, 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Patients with PCSK9I exposure within 1 year before ICI treatment initiation were compared with those receiving high-intensity statins without PCSK9I use. One-to-one propensity score matching was performed, followed by Kaplan-Meier and Cox proportional hazards regression analyses.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were overall survival and a modified 4-point major adverse cardiovascular event (MACE) composite. Secondary outcomes included use of acute health care services (emergency department visits, hospitalization, and critical care services).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 239 matched pairs of patients (478 patients; 273 [57.1%] male; mean [SD] age, 70.8 [8.5] years), the mean (SD) age was 70.7 (8.2) years in the PCSK9I cohort and 70.8 (8.7) years in the statin cohort; lung cancer was the most common malignant neoplasm (159 [66.5%] vs 150 [62.8%], respectively). During follow-up as long as 9 years, 99 deaths occurred in the PCSK9I cohort and 129 in the statin-only cohort. PCSK9I use was associated with improved survival (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; log-rank\n P<\/jats:italic>\n \u2009=\u2009.006), with 2-year survival probabilities of 62% vs 51%. MACE did not differ significantly (73 vs 81 events; HR, 0.85; 95% CI, 0.62-1.16;\n P<\/jats:italic>\n \u2009=\u2009.31). PCSK9I use was also associated with lower risks of emergency department visits (HR, 0.65; 95% CI, 0.49-0.86;\n P<\/jats:italic>\n \u2009=\u2009.002), hospitalization (HR, 0.73; 95% CI, 0.57-0.92;\n P<\/jats:italic>\n \u2009=\u2009.008), and use of critical care services (HR, 0.68; 95% CI, 0.48-0.96;\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Among adults with non\u2013small cell lung cancer, melanoma, or renal cell carcinoma receiving ICIs, PCSK9I use was associated with improved survival and reduced levels of acute health care utilization without significant differences in cardiovascular events, warranting further prospective investigation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.12707","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:30:18Z","timestamp":1780068618000},"page":"e2612707","source":"Crossref","is-referenced-by-count":0,"title":["Use of PCSK9 Inhibitors Among Patients Receiving Immune Checkpoint Inhibitors for Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Chuan Angel","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changchuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas"},{"name":"Peter O\u2019Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Z.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"issue":"1","key":"zoi260382r1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-024-02212-7","article-title":"Resistance mechanisms to immune checkpoint inhibitors: updated insights.","volume":"24","author":"Alsaafeen","year":"2025","journal-title":"Mol Cancer"},{"issue":"4","key":"zoi260382r2","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.ccell.2020.03.017","article-title":"Acquired resistance to immune checkpoint inhibitors.","volume":"37","author":"Schoenfeld","year":"2020","journal-title":"Cancer Cell"},{"issue":"1","key":"zoi260382r3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41392-023-01690-3","article-title":"Targeting proprotein convertase subtilisin\/kexin type 9 (PCSK9): from bench to bedside.","volume":"9","author":"Bao","year":"2024","journal-title":"Signal Transduct Target Ther"},{"issue":"7839","key":"zoi260382r4","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41586-020-2911-7","article-title":"Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer.","volume":"588","author":"Liu","year":"2020","journal-title":"Nature"},{"issue":"7","key":"zoi260382r5","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70403","article-title":"Decoding MHC loss: molecular mechanisms and implications for immune resistance in cancer.","volume":"15","author":"Lin","year":"2025","journal-title":"Clin Transl Med"},{"issue":"1","key":"zoi260382r6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41392-021-00530-6","article-title":"Targeting PCSK9: a promising adjuvant strategy in cancer immunotherapy.","volume":"6","author":"Almeida","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"zoi260382r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175721","article-title":"The evolving landscape of PCSK9 inhibition in cancer.","volume":"949","author":"Oza","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"zoi260382r11","doi-asserted-by":"publisher","first-page":"0488","DOI":"10.34133\/research.0488","article-title":"Inhibition of PCSK9: a promising enhancer for anti-pd-1\/pd-l1 immunotherapy.","volume":"7","author":"Sun","year":"2024","journal-title":"Research"},{"issue":"2","key":"zoi260382r12","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad035","article-title":"A global federated real-world data and analytics platform for research.","volume":"6","author":"Palchuk","year":"2023","journal-title":"JAMIA Open"},{"issue":"1","key":"zoi260382r13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.","volume":"41","author":"Mach","year":"2020","journal-title":"Eur Heart J"},{"issue":"1","key":"zoi260382r14","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1186\/s12874-021-01440-5","article-title":"Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review.","volume":"21","author":"Bosco","year":"2021","journal-title":"BMC Med Res Methodol"},{"issue":"10","key":"zoi260382r15","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1161\/CIRCULATIONAHA.119.041022","article-title":"Impact of regulatory guidance on evaluating cardiovascular risk of new glucose-lowering therapies to treat type 2 diabetes mellitus: lessons learned and future directions.","volume":"141","author":"Sharma","year":"2020","journal-title":"Circulation"},{"key":"zoi260382r16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jare.2024.03.017","article-title":"Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers.","volume":"69","author":"Guan","year":"2025","journal-title":"J Adv Res"},{"issue":"7","key":"zoi260382r17","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1001\/jama.2020.9151","article-title":"Immortal time bias in observational studies.","volume":"325","author":"Yadav","year":"2021","journal-title":"JAMA"},{"issue":"23","key":"zoi260382r18","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1161\/CIRCULATIONAHA.117.028430","article-title":"Proprotein convertase subtilisin\/kexin type 9 inhibitor therapy: payer approvals and rejections, and patient characteristics for successful prescribing.","volume":"136","author":"Hess","year":"2017","journal-title":"Circulation"},{"key":"zoi260382r19","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1516126","article-title":"A comprehensive review of methodologies and application to use the real-world data and analytics platform TriNetX.","volume":"16","author":"Ludwig","year":"2025","journal-title":"Frontiers Pharmacol"},{"key":"zoi260382r8","unstructured":"A phase II study of PCSK9 inhibitor alirocumab and PD-1 inhibitor cemiplimab in patients with metastatic, refractory to prior anti-PD-1 non\u2013small cell lung cancer (TOP2201). ClinicalTrials.gov identifier: NCT05553834. Updated January 22, 2026. Accessed March 16, 2026. https:\/\/clinicaltrials.gov\/study\/NCT05553834"},{"key":"zoi260382r9","unstructured":"Safety, efficacy, and tumor immune microenvironment changes with neoadjuvant chemotherapy and cemiplimab with or without alirocumab in stage IB\u2013IIIA non\u2013small cell lung cancer (TOP2301). ClinicalTrials.gov identifier: NCT06385262. Updated March 6, 2026. Accessed March 16, 2026. https:\/\/clinicaltrials.gov\/study\/NCT06385262"},{"key":"zoi260382r10","unstructured":"A phase II study bolstering outcomes by optimizing immunotherapy strategies with evolocumab and nivolumab in patients with metastatic renal cell carcinoma (BOOST-RCC). ClinicalTrials.gov identifier: NCT06284564. Updated March 4, 2026. Accessed March 16, 2026. https:\/\/clinicaltrials.gov\/study\/NCT06284564"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2849633\/lu_2026_oi_260382_1779387088.35358.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:30:20Z","timestamp":1780068620000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2849633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.12707","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}