C K Mapendano, A K Nøhr, M Sønderkær, A Pagh, A Carus, T Lörincz, C A Haslund, L Ø Poulsen, A Ernst, J S Bødker, S C Dahl, L Sunde, A H Brügmann, C Vesteghem, I S Pedersen, M Ladekarl
{"title":"在晚期癌症患者中使用精准药物延长生存期。","authors":"C K Mapendano, A K Nøhr, M Sønderkær, A Pagh, A Carus, T Lörincz, C A Haslund, L Ø Poulsen, A Ernst, J S Bødker, S C Dahl, L Sunde, A H Brügmann, C Vesteghem, I S Pedersen, M Ladekarl","doi":"10.1016/j.esmoop.2024.104089","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.</p><p><strong>Materials and methods: </strong>Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.</p><p><strong>Results: </strong>One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.</p><p><strong>Conclusions: </strong>Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104089"},"PeriodicalIF":7.1000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longer survival with precision medicine in late-stage cancer patients.\",\"authors\":\"C K Mapendano, A K Nøhr, M Sønderkær, A Pagh, A Carus, T Lörincz, C A Haslund, L Ø Poulsen, A Ernst, J S Bødker, S C Dahl, L Sunde, A H Brügmann, C Vesteghem, I S Pedersen, M Ladekarl\",\"doi\":\"10.1016/j.esmoop.2024.104089\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.</p><p><strong>Materials and methods: </strong>Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.</p><p><strong>Results: </strong>One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.</p><p><strong>Conclusions: </strong>Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.</p>\",\"PeriodicalId\":11877,\"journal\":{\"name\":\"ESMO Open\",\"volume\":\"10 1\",\"pages\":\"104089\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ESMO Open\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.esmoop.2024.104089\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ESMO Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.esmoop.2024.104089","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Longer survival with precision medicine in late-stage cancer patients.
Background: In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.
Materials and methods: Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.
Results: One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.
Conclusions: Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.
期刊介绍：
ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research.
ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO.
Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.
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