{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:58:16Z","timestamp":1793177896935,"version":"4.5.0"},"reference-count":19,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"24","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,8,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04071223\">NCT04071223<\/jats:ext-link>\n                      ) evaluated cabozantinib \u00b1 radium-223 in mRCC with BM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This phase II trial enrolled patients with mRCC of any histology with \u22651 BM. Patients were randomly assigned 1:1 to cabozantinib \u00b1 radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) &gt; 1.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .78). Grade \u22653 adverse events were similar across arms (69.6%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      75.5%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-01135","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:00:00Z","timestamp":1785182400000},"page":"2341-2352","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801)"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-7963","authenticated-orcid":false,"given":"Rana R.","family":"McKay","sequence":"first","affiliation":[{"name":"University of California San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4492-0357","authenticated-orcid":false,"given":"Karla 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