{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:37:36Z","timestamp":1792183056293,"version":"4.4.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              The use of immune checkpoint inhibitors (ICPIs) has expanded in the treatment of metastatic urothelial carcinoma (mUC), but response rates are variable, highlighting the need for predictive biomarkers. Tumor mutational burden (TMB) has been shown to predict response to ICPI, but Fibroblast Growth Factor Receptor 3 (\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              ) alterations are common drivers in mUC and there is preclinical and anecdotal evidence that they may predict less favorable outcomes to ICPIs, similar to\n              <jats:italic toggle=\"yes\">ALK<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">ROS1<\/jats:italic>\n              fusions in lung cancer. We sought to explore the effect of\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              alterations alone and with TMB on response to ICPI in mUC.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              A total of 1,416 patients with mUC who received hybrid-capture next-generation sequencing (NGS)-based genomic profiling were evaluated for their response to ICPI and chemotherapy based on the presence of\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              alterations and TMB. A nationwide deidentified real-world clinicogenomic database (CGDB) of NGS results linked to deidentified electronic health record\u2013derived clinical data was used to assess treatment patterns and real-world overall survival (rwOS) and real-world progression-free survival (rwPFS).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Among 819 patients with mUC who received ICPI, there were no significant differences in rwOS or rwPFS between\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              -altered (alt) and wild-type (wt) patients. However, among patients with TMB \u226510 mut\/Mb,\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              -alt patients trended toward longer rwOS and rwPFS than\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              -wt patients. Comparing first-line ICPI versus chemotherapy and adjusting for imbalances, patients with TMB \u226510 and\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              -alt who received ICPI also trended toward longer rwPFS than patients who received chemotherapy although no significant difference in rwOS was observed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              While\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              status alone is not predictive of response to ICPI,\n              <jats:italic toggle=\"yes\">FGFR3<\/jats:italic>\n              combined with TMB emerged as a biomarker that may be predictive of response to ICPI in mUC. Further studies involving larger patient populations are warranted to confirm these findings.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-25-00257","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:59:28Z","timestamp":1758052768000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Fibroblast Growth Factor Receptor 3 Alteration Status and Outcomes on Immune Checkpoint Inhibitors in Patients With Metastatic Urothelial Carcinoma"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-503X","authenticated-orcid":true,"given":"Shilpa","family":"Gupta","sequence":"first","affiliation":[{"name":"Cleveland Clinic Taussig Cancer Institute, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-5092","authenticated-orcid":true,"given":"Jessica K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8029-8788","authenticated-orcid":true,"given":"Jerry","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8395-5168","authenticated-orcid":true,"given":"Richard S.P.","family":"Huang","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9020015"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2017.190"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00152-2"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30230-0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30445-9"},{"key":"e_1_3_4_8_2","article-title":"Tumor mutational burden as a predictor of first-line immune checkpoint inhibitor versus carboplatin benefit in cisplatin-unfit patients with urothelial carcinoma","author":"Graf RP","unstructured":"Graf RP, Fisher V, Huang RSP, et al: Tumor mutational burden as a predictor of first-line immune checkpoint inhibitor versus carboplatin benefit in cisplatin-unfit patients with urothelial carcinoma. JCO Precis Oncol 10.1200\/PO.22.00121","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3817"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt419"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817323"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308849"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13753"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01579-0"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.06.025"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1221718"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01488-6"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.003"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.3241"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2696"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0264138"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237802"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00987"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0595"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01761-7"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T19:59:34Z","timestamp":1758052774000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1200\/PO-25-00257"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00257","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500257"}}