{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:34:36Z","timestamp":1788053676378,"version":"build-2784847793"},"reference-count":57,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Avelumab first\u2010line (1\u2009L) maintenance is a standard of care for advanced urothelial carcinoma (aUC) based on the JAVELIN Bladder 100 phase 3 trial, which showed that avelumab 1\u2009L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression\u2010free survival (PFS) vs BSC alone in patients who were progression free after receiving 1\u2009L platinum\u2010containing chemotherapy. Here, we comprehensively screened JAVELIN Bladder 100 trial datasets to identify prognostic factors that define subpopulations of patients with longer or shorter OS irrespective of treatment, and predictive factors that select patients who could obtain a greater OS benefit from avelumab 1\u2009L maintenance treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed machine learning analyses to screen a large set of baseline covariates, including patient demographics, disease characteristics, laboratory values, molecular biomarkers, and patient\u2010reported outcomes. Covariates were identified from previously reported analyses and established prognostic and predictive markers. Variables selected from random survival forest models were processed further in univariate Cox models with treatment interaction and visually inspected using correlation analysis and Kaplan\u2013Meier curves. Results were summarized in a multivariable Cox model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Prognostic baseline covariates associated with OS included in the final model were assignment to avelumab 1\u2009L maintenance treatment, Eastern Cooperative Oncology Group performance status, site of metastasis, sum of longest target lesion diameters, levels of C\u2010reactive protein and alkaline phosphatase in blood, lymphocyte proportion in intratumoral stroma, tumor mutational burden, and tumor CD8+ T\u2010cell infiltration. Potential predictive factors included site of metastasis, tumor mutation burden, and tumor CD8+ T\u2010cell infiltration. An analysis in patients with PD\u2010L1+ tumors had similar findings to those in the overall population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Machine learning analyses of data from the JAVELIN Bladder 100 trial identified potential prognostic and predictive factors for avelumab 1\u2009L maintenance treatment in patients with aUC, which warrant further evaluation in other clinical datasets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.7411","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T06:21:51Z","timestamp":1719210111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Avelumab first\u2010line maintenance in advanced urothelial carcinoma: Complete screening for prognostic and predictive factors using machine learning in the\n                    <scp>JAVELIN<\/scp>\n                    Bladder 100 phase 3 trial"],"prefix":"10.1002","volume":"13","author":[{"given":"Juliane","family":"Manitz","sequence":"first","affiliation":[{"name":"EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslihan","family":"Gerhold\u2010Ay","sequence":"additional","affiliation":[{"name":"The healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0853-9364","authenticated-orcid":false,"given":"Pascal","family":"Kieslich","sequence":"additional","affiliation":[{"name":"The healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parantu","family":"Shah","sequence":"additional","affiliation":[{"name":"EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mrowiec","sequence":"additional","affiliation":[{"name":"The healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Tyroller","sequence":"additional","affiliation":[{"name":"EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","first-page":"15","article-title":"Epidemiology of bladder cancer","volume":"8","author":"Saginala K","year":"2020","journal-title":"Med Sci (Basel)"},{"key":"e_1_2_11_3_1","unstructured":"National Cancer Institute.SEER Cancer Stat Facts: Bladder Cancer. 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