JAMA Oncology最新文献

{"title":"Clinical Value of Molecular Targets and FDA-Approved Genome-Targeted Cancer Therapies","authors":"Ariadna Tibau, Thomas J. Hwang, Consolacion Molto, Jerry Avorn, Aaron S. Kesselheim","doi":"10.1001/jamaoncol.2024.0194","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.0194","url":null,"abstract":"ImportanceThe number of new genome-targeted cancer drugs has increased, offering the possibility of personalized therapy, often at a very high cost.ObjectiveTo assess the validity of molecular targets and therapeutic benefits of US Food and Drug Administration–approved genome-targeted cancer drugs based on the outcomes of their corresponding pivotal clinical trials.Design and SettingsIn this cohort study, all genome-targeted cancer drugs that were FDA-approved between January 1, 2015, and December 31, 2022, were analyzed. From FDA drug labels and trial reports, key characteristics of pivotal trials were extracted, including the outcomes assessed.Main Outcomes and MeasuresThe strength of evidence supporting molecular targetability was assessed using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). Clinical benefit for their approved indications was evaluated using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS). Substantial clinical benefit was defined as a grade of A or B for curative intent and 4 or 5 for noncurative intent. Molecular targets qualifying for ESCAT category level I-A and I-B associated with substantial clinical benefit by ESMO-MCBS were rated as high-benefit genomic-based cancer treatments.ResultsA total of 50 molecular-targeted drugs covering 84 indications were analyzed. Forty-five indications (54%) were approved based on phase 1 or phase 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials, and 48 (57%) were approved on the basis of subgroup analyses. By each indication, 46 of 84 primary end points (55%) were overall response rate (median [IQR] overall response rate, 57% [40%-69%]; median [IQR] duration of response, 11.1 [9.2-19.8] months). Among the 84 pivotal trials supporting these 84 indications, 38 trials (45%) had I-A ESCAT targetability, and 32 (38%) had I-B targetability. Overall, 24 of 84 trials (29%) demonstrated substantial clinical benefit via ESMO-MCBS. Combining these ratings, 24 of 84 indications (29%) were associated with high-benefit genomic-based cancer treatments.Conclusions and RelevanceThe results of this cohort study demonstrate that among recently approved molecular-targeted cancer therapies, fewer than one-third demonstrated substantial patient benefits at approval. Benefit frameworks such as ESMO-MCBS and ESCAT can help physicians, patients, and payers identify therapies with the greatest clinical potential.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"28 15 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Error in Visual Abstract.","authors":"","doi":"10.1001/jamaoncol.2021.5278","DOIUrl":"10.1001/jamaoncol.2021.5278","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":"541"},"PeriodicalIF":28.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39444125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAMA Oncology.","authors":"","doi":"10.1001/jamaoncol.2021.5526","DOIUrl":"https://doi.org/10.1001/jamaoncol.2021.5526","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 11 1","pages":"1543"},"PeriodicalIF":28.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43029651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Trial and Real-world Adjuvant Oxaliplatin Delivery in Patients With Stage III Colon Cancer Using a Longitudinal Cumulative Dose.","authors":"Michael Webster-Clark, Alexander P Keil, Nicholas Robert, Jennifer R Frytak, Marley Boyd, Til Stürmer, Hanna Sanoff, Daniel Westreich, Jennifer L Lund","doi":"10.1001/jamaoncol.2022.4445","DOIUrl":"10.1001/jamaoncol.2022.4445","url":null,"abstract":"<p><strong>Importance: </strong>Delivery of adjuvant chemotherapy can differ substantially between trial and real-world populations. Adherence metrics like relative dose intensity (RDI) cannot capture the timing of modifications and mask differences in the total amount of chemotherapy received.</p><p><strong>Objective: </strong>To compare oxaliplatin delivery between MOSAIC trial participants and patients treated in the US Oncology Network with stage III colon cancer using a longitudinal cumulative dose (LCD).</p><p><strong>Design, setting, and participants: </strong>This cohort study used secondary data from the MOSAIC trial, an international randomized clinical trial (concluded in 2004), and electronic health records from US Oncology (2009-2018), a network of community oncology practices in the US. It included participants in MOSAIC with stage III colon cancer who were randomized to receive treatment with oxaliplatin and fluorouracil/leucovorin (n = 663) and US Oncology patients with stage III colon cancer who were treated with a modified FOLFOX-6 regimen (n = 2523).</p><p><strong>Exposures: </strong>Oxaliplatin and fluorouracil/leucovorin.</p><p><strong>Outcomes and measures: </strong>We evaluated RDI and LCD over time and at the end of treatment in the MOSAIC and US Oncology populations. We used bootstrapping to estimate 95% confidence bands for LCD differences between the populations.</p><p><strong>Results: </strong>The 663 MOSAIC participants (296 women [44.7%]) and 2523 US Oncology patients (1245 women [49.4%]) were generally similar with respect to demographic characteristics. Median RDI was lower in US Oncology (80% in MOSAIC vs 70% in US Oncology). The LCD also suggested differences in the total amount of oxaliplatin received between populations; the final median LCD in US Oncology was 10.2% lower than in MOSAIC, equivalent to receiving 1.2 fewer treatment cycles less of oxaliplatin. This difference only began 133 days into treatment and persisted after accounting for covariates, likely in terms of more frequent oxaliplatin treatment discontinuation in US Oncology patients than their MOSAIC counterparts.</p><p><strong>Conclusions and relevance: </strong>The study results suggest that real-world patients in community practice in the US treated with modified FOLFOX 6 received less oxaliplatin than their historical counterparts in the MOSAIC trial, with differences manifesting late in the treatment course. The LCD allowed us to identify the amount and extent of these differences, the timing of which was unclear when using RDI alone.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT00275210.</p>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of 5α-Reductase Inhibitor Use With Prostate Cancer-Specific Mortality-Reply.","authors":"Lars Björnebo, Martin Eklund, Anna Lantz","doi":"10.1001/jamaoncol.2022.4792","DOIUrl":"10.1001/jamaoncol.2022.4792","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cast of Shadow on Postoperative Radiotherapy for pIIIA-N2 Non-Small Cell Lung Cancer?","authors":"Stefania Canova, Stefano Arcangeli, Diego Luigi Cortinovis","doi":"10.1001/jamaoncol.2022.4442","DOIUrl":"10.1001/jamaoncol.2022.4442","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33505407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-Associated Breast Cancer Following Childhood Cancer: Where Do We Go From Here?","authors":"Kelsey L Corrigan, Michael Roth","doi":"10.1001/jamaoncol.2022.4590","DOIUrl":"10.1001/jamaoncol.2022.4590","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of 5α-Reductase Inhibitor Use With Prostate Cancer-Specific Mortality.","authors":"Hein V Stroomberg, Klaus Brasso, Andreas Røder","doi":"10.1001/jamaoncol.2022.4789","DOIUrl":"10.1001/jamaoncol.2022.4789","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33504847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Errors in Abstract and Affiliations.","authors":"","doi":"10.1001/jamaoncol.2022.4267","DOIUrl":"https://doi.org/10.1001/jamaoncol.2022.4267","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 10","pages":"1518"},"PeriodicalIF":28.4,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutaminase Inhibitors-Do They Have a Role in the Treatment of Metastatic Clear-Cell Renal Cell Carcinoma?","authors":"Janet E Brown","doi":"10.1001/jamaoncol.2022.3378","DOIUrl":"https://doi.org/10.1001/jamaoncol.2022.3378","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 10","pages":"1418-1419"},"PeriodicalIF":28.4,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40336717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}