{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:35:40Z","timestamp":1783391740826,"version":"3.54.6"},"reference-count":8,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>HIF-2\u03b1 signaling is a central driver of clear cell renal cell carcinoma biology. With regulatory approval of the HIF-2\u03b1 inhibitor, belzutifan, in the third- and fourth-line refractory setting, therapeutic targeting of this pathway has entered clinical practice. At the 2026 ASCO GU Cancer Symposium, two randomized phase III trials evaluated earlier integration of belzutifan: LITESPARK-022 (belzutifan plus pembrolizumab vs pembrolizumab alone in the adjuvant setting) and LITESPARK-011 (belzutifan plus lenvatinib vs cabozantinib in the post-PD-(L)1 setting). LITESPARK-022 demonstrated a disease-free survival benefit (HR 0.72; 95% CI, 0.59-0.87; P\u2009=\u2009.0003), with early and sustained curve separation, though grade \u22653 adverse events doubled and overall survival data remain immature. LITESPARK-011 enrolled patients after progression on prior PD-(L)1 therapy in the metastatic setting. The combination improved median progression-free survival (PFS; 14.8 vs 10.7\u2009months; HR 0.70), objective response rate (ORR; 52.6% vs 40%), and duration of response (23 vs 12\u2009months), with a manageable toxicity profile. Together, these studies suggest that earlier targeting of HIF-2\u03b1 biology may improve disease control and durability. However, patient selection, toxicity considerations, and the absence of mature OS data remain critical factors in determining the optimal role of belzutifan-based strategies across disease states.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag193","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:04:31Z","timestamp":1778760271000},"source":"Crossref","is-referenced-by-count":1,"title":["From prevention to progression: can belzutifan-based strategies deliver across the RCC disease continuum?"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-6140","authenticated-orcid":false,"given":"Kathryn","family":"Beckermann","sequence":"first","affiliation":[{"name":"Medical Director of GU Clinical Research, Greco-Hainsworth Center for Research, Tennessee Oncology , Nashville, TN 37203,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"2026060806364247600_oyag193-B1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.semcancer.2012.06.001","article-title":"The VHL\/HIF axis in clear cell renal carcinoma","volume":"23","author":"Shen","year":"2013","journal-title":"Semin Cancer Biol"},{"key":"2026060806364247600_oyag193-B2","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1056\/NEJMoa2313906","article-title":"Belzutifan versus everolimus for advanced renal-cell carcinoma","volume":"391","author":"Choueiri","year":"2024","journal-title":"N Engl J Med"},{"key":"2026060806364247600_oyag193-B3","doi-asserted-by":"publisher","first-page":"LBA418","DOI":"10.1200\/JCO.2026.44.7_suppl.LBA418","article-title":"Adjuvant pembrolizumab plus belzutifan versus pembrolizumab for clear cell renal cell carcinoma (ccRCC): the randomized phase 3 LITESPARK-022 study [abstract LBA418]","volume":"44","author":"Choueiri","year":"2026","journal-title":"J Clin Oncol"},{"key":"2026060806364247600_oyag193-B4","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1056\/NEJMoa2312695","article-title":"Overall survival with adjuvant pembrolizumab in renal-cell carcinoma","volume":"390","author":"Choueiri","year":"2024","journal-title":"N Engl J Med"},{"key":"2026060806364247600_oyag193-B5","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S0140-6736(23)00922-4","article-title":"Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial","volume":"402","author":"Pal","year":"2023","journal-title":"Lancet"},{"key":"2026060806364247600_oyag193-B6","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/S0140-6736(24)01758-6","article-title":"Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 study","volume":"404","author":"Choueiri","year":"2024","journal-title":"Lancet"},{"key":"2026060806364247600_oyag193-B7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.annonc.2025.10.009","article-title":"A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear-cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo)","volume":"37","author":"Hahn","year":"2026","journal-title":"Ann Oncol"},{"issue":"suppl","key":"2026060806364247600_oyag193-B8","first-page":"LBA417","article-title":"Belzutifan plus lenvatinib versus cabozantinib for advanced renal cell carcinoma after anti-PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study [abstract LBA417]","volume":"44","author":"Motzer","year":"2026","journal-title":"J Clin Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag193\/68307947\/oyag193.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/7\/oyag193\/68307947\/oyag193.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/7\/oyag193\/68307947\/oyag193.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:36:49Z","timestamp":1780915009000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyag193\/8681580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,16]]},"references-count":8,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,6,6]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag193","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,5,16]]},"article-number":"oyag193"}}