{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:12:33Z","timestamp":1792087953932,"version":"4.4.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Patients with clinical T2-4aN0\/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once on day 1, and gemcitabine 1,000 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (&lt; pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved &lt; pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.01003","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T15:59:55Z","timestamp":1629820795000},"page":"3140-3148","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":133,"title":["Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-2487","authenticated-orcid":false,"given":"Tracy L.","family":"Rose","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC"},{"name":"Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, 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