{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:43:39Z","timestamp":1745815419621},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Clinical Cancer Informatics"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Drug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Seventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I trials in multiple myeloma, but not the success rate, significantly increased over the period studied. The proportion of industry-sponsored trials also steadily increased over that same period. The ratio of initial dose to maximum tolerated dose was 0.29, suggesting that many patients were undertreated. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Investigational agents with higher ORRs in phase I trials were more likely to advance to phase II trials and achieve US Food and Drug Administration approval. Our results suggest that designing phase I trials to maximize the antimyeloma efficacy of a given compound may lead to more successful and cost-effective drug development. <\/jats:p><\/jats:sec>","DOI":"10.1200\/cci.17.00055","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T20:55:15Z","timestamp":1510260915000},"page":"1-14","update-policy":"http:\/\/dx.doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Predicting Successful Phase Advancement and Regulatory Approval in Multiple Myeloma From Phase I Overall Response Rates"],"prefix":"10.1200","author":[{"given":"Ehsan","family":"Malek","sequence":"first","affiliation":[{"name":"Ehsan Malek, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, University Hospitals Seidman Cancer Center; Ehsan Malek, Byung-Gyu Kim, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. Driscoll, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caner","family":"Saygin","sequence":"additional","affiliation":[{"name":"Ehsan Malek, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, University Hospitals Seidman Cancer Center; Ehsan Malek, Byung-Gyu Kim, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. Driscoll, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Ye","sequence":"additional","affiliation":[{"name":"Ehsan Malek, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, University Hospitals Seidman Cancer Center; Ehsan Malek, Byung-Gyu Kim, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. Driscoll, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahrettin","family":"Covut","sequence":"additional","affiliation":[{"name":"Ehsan Malek, Fahrettin Covut, Neal J. 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Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. Driscoll, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Welge","sequence":"additional","affiliation":[{"name":"Ehsan Malek, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, University Hospitals Seidman Cancer Center; Ehsan Malek, Byung-Gyu Kim, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. 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