BMJ Oncology最新文献_第2页

Assessing patient risk, benefit and outcomes in drug development: an observational study of regorafenib clinical trials 评估药物开发中的患者风险、获益和结果：瑞戈非尼临床试验观察研究

BMJ Oncology Pub Date : 2024-03-01 DOI: 10.1136/bmjonc-2023-000229

Brody Dennis, Chance Bratten, Griffin K. Hughes, Andriana Peña, Ryan McIntire, Chase Ladd, Brooke Gardner, William Nowlin, Reagan Livingston, J. Tuia, A. Haslam, Vinay Prasad, Matt Vassar

{"title":"Assessing patient risk, benefit and outcomes in drug development: an observational study of regorafenib clinical trials","authors":"Brody Dennis, Chance Bratten, Griffin K. Hughes, Andriana Peña, Ryan McIntire, Chase Ladd, Brooke Gardner, William Nowlin, Reagan Livingston, J. Tuia, A. Haslam, Vinay Prasad, Matt Vassar","doi":"10.1136/bmjonc-2023-000229","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000229","url":null,"abstract":"Our objective of this study was to analyse all oncological clinical trials using regorafenib to create a complete risk/benefit profile for the drug.Creating a novel chemotherapy is costly both in time and capital spent for drug manufacturers. To regenerate what they’ve spent, drug manufacturers may attempt to repurpose their medications for new indications via clinical trials. To fully understand the risk/benefits in comparison to a drug’s efficacy, a pooled analysis must be completed.We screened PubMed, Embase, Cochrane (CENTRAL) and ClinicalTrials.gov for trials of regorafenib used to treat solid cancers. Next, we extracted median progression-free survival and overall survival in months, adverse event rates and objective response rate (ORR). Studies were deemed positive, negative or indeterminate based on their pre-specified endpoints and tolerability.56 clinical trials were included in our final sample, with 4960 total participants across 13 indications. Most studies (44 of 56; 78.75%) were non-blinded, and a majority were non-randomised (41 of 56; 73.21%). Trials for colorectal cancer started out as positive but became more negative over time. Cumulative risk to patients increased over time while ORR stayed consistently low.Our findings suggest that since regorafenib’s original Food and Drug Administration (FDA) approval, the risk profile for its original indication increased. The amount of non-randomised, single-arm trials in our sample size was concerning, indicating that higher quality research must be conducted. Our results propose that regorafenib’s efficacy and safety may be more impactful in cancers other than its FDA approvals.","PeriodicalId":505335,"journal":{"name":"BMJ Oncology","volume":"139 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning predicted fast progression after initiation of immune checkpoint inhibitors in advanced non-small cell lung cancer 机器学习预测晚期非小细胞肺癌患者开始使用免疫检查点抑制剂后的快速进展

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000227

Y. Soon, Teng Hwee Tan, Chee Khoon Lee, Martin Stockler

引用次数: 0

Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity 癌症中的低氧诱导因子：从通路调控到治疗机会

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000154

Brian M Ortmann

{"title":"Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity","authors":"Brian M Ortmann","doi":"10.1136/bmjonc-2023-000154","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000154","url":null,"abstract":"Cancer remains one of the most formidable challenges in modern medicine, due to its complex and dynamic nature, which demands innovative therapeutic approaches. One major challenge to cancer treatment is the tumour microenvironment and in particular tumour hypoxia (low oxygen levels), which contributes to tumour progression and immune evasion. At the cellular level, this is primarily governed by hypoxia-inducible factor (HIF). HIF is a transcription factor that orchestrates cellular responses to low oxygen levels, driving angiogenesis, metabolic adaptation and immune regulation. HIF’s dysregulation is frequently observed in various cancer types and correlates with increased aggressiveness, metastasis, resistance to therapy and poor patient prognosis. Consequently, understanding the cellular mechanisms underlying HIF activation and its downstream effects has become crucial to developing targeted cancer therapies for improving cancer patient outcomes and represents a key step towards precision medicine.Recent advancements in drug development have led to the emergence of HIF inhibitors, which aim to disrupt HIF-driven processes in cancer providing therapeutic benefit. Here, we provide a review of the molecular mechanisms through which HIF promotes tumour growth and resistance, emphasising the potential clinical benefits of HIF-targeted therapies. This review will discuss the challenges and opportunities associated with translating HIF inhibition into clinical practice, including ongoing clinical trials and future directions in the development of HIF-based cancer treatments.","PeriodicalId":505335,"journal":{"name":"BMJ Oncology","volume":"13 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139818070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning based on blood test biomarkers predicts fast progression in advanced NSCLC patients treated with immunotherapy 基于血液检测生物标志物的机器学习可预测接受免疫疗法的晚期非小细胞肺癌患者病情的快速进展

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000128

Jian-Guo Zhou, Jie Yang, Haitao Wang, Ada Hang-Heng Wong, Fangya Tan, Xiaofei Chen, Sisi He, Gang Shen, Yun-Jia Wang, Benjamin Frey, R. Fietkau, M. Hecht, Wenzhao Zhong, Hu Ma, U. Gaipl

{"title":"Machine learning based on blood test biomarkers predicts fast progression in advanced NSCLC patients treated with immunotherapy","authors":"Jian-Guo Zhou, Jie Yang, Haitao Wang, Ada Hang-Heng Wong, Fangya Tan, Xiaofei Chen, Sisi He, Gang Shen, Yun-Jia Wang, Benjamin Frey, R. Fietkau, M. Hecht, Wenzhao Zhong, Hu Ma, U. Gaipl","doi":"10.1136/bmjonc-2023-000128","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000128","url":null,"abstract":"Fast progression (FP) represents a desperate situation for advanced non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor therapy. We aimed to develop a predictive framework based on machine learning (ML) methods to identify FP in advanced NSCLC patients using blood test biomarkers.We extracted data of 1546 atezolizumab-treated patients from four multicentre clinical trials. In this study, patients from the OAK trial were taken for model training, whereas patients from the other trials were used for independent validations. The FP prediction model was developed using 21 pretreatment blood test variables in seven ML approaches. Prediction performance was evaluated by the receiver operating characteristic (ROC) curve.The prevalence of FP was 7.6% (118 of 1546) in all atezolizumab-treated patients. The most important variables for the prediction model were: C reactive protein, neutrophil count, lactate dehydrogenase and alanine transaminase. The Support Vector Machine (SVM) algorithm applied to these four blood test parameters demonstrated good performance: the area under the ROC curve obtained from the training cohort (OAK), validation cohort 1 (BIRCH) and cohort 2 (merged POPLAR and FIR) were 0.908, 0.666 and 0.776, respectively. In addition, the absolute difference in median survival between the SVM-predicted FP and non-FP groups was significant in both progression-free survival and overall survival (p<0.001).SVM trained using a 4-biomarker panel has good performance in predicting the occurrence of FP regardless of programmed cell death ligand 1 expression, hence providing evidence for decision-making in single-agent atezolizumab immunotherapy for patients with advanced NSCLC.","PeriodicalId":505335,"journal":{"name":"BMJ Oncology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139685207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Time, location and function of hypoxia-inducible factors are critical to therapeutic tumour response 缺氧诱导因子的时间、位置和功能对肿瘤治疗反应至关重要

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000290

Laure Marignol, C. Pugh

引用次数: 0

Cervical cancer screening using tests that provide same-day results: a study of test accuracy 使用当天出结果的检验方法进行宫颈癌筛查：检验准确性研究

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000234

L. Denny

引用次数: 0

Cervical cancer screening using tests that provide same-day results: a study of test accuracy 使用当天出结果的检验方法进行宫颈癌筛查：检验准确性研究

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000234

L. Denny

引用次数: 0

Identifying the deficits in cancer care for people with intellectual disabilities 找出智障人士癌症护理的不足之处

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000171

Maarten Cuypers, Deborah Cairns, Kathryn A. Robb

引用次数: 0

Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity 癌症中的低氧诱导因子：从通路调控到治疗机会

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000154

Brian M Ortmann

{"title":"Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity","authors":"Brian M Ortmann","doi":"10.1136/bmjonc-2023-000154","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000154","url":null,"abstract":"Cancer remains one of the most formidable challenges in modern medicine, due to its complex and dynamic nature, which demands innovative therapeutic approaches. One major challenge to cancer treatment is the tumour microenvironment and in particular tumour hypoxia (low oxygen levels), which contributes to tumour progression and immune evasion. At the cellular level, this is primarily governed by hypoxia-inducible factor (HIF). HIF is a transcription factor that orchestrates cellular responses to low oxygen levels, driving angiogenesis, metabolic adaptation and immune regulation. HIF’s dysregulation is frequently observed in various cancer types and correlates with increased aggressiveness, metastasis, resistance to therapy and poor patient prognosis. Consequently, understanding the cellular mechanisms underlying HIF activation and its downstream effects has become crucial to developing targeted cancer therapies for improving cancer patient outcomes and represents a key step towards precision medicine.Recent advancements in drug development have led to the emergence of HIF inhibitors, which aim to disrupt HIF-driven processes in cancer providing therapeutic benefit. Here, we provide a review of the molecular mechanisms through which HIF promotes tumour growth and resistance, emphasising the potential clinical benefits of HIF-targeted therapies. This review will discuss the challenges and opportunities associated with translating HIF inhibition into clinical practice, including ongoing clinical trials and future directions in the development of HIF-based cancer treatments.","PeriodicalId":505335,"journal":{"name":"BMJ Oncology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139878065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review 恩扎鲁胺、阿帕鲁胺或达罗鲁胺治疗转移性前列腺癌的标准剂量和减量剂量比较：快速综述

BMJ Oncology Pub Date : 2024-02-01 DOI: 10.1136/bmjonc-2023-000198

Hannah Louise Bromley, Mohini Varughese, Duncan C Gilbert, Peter J Hoskin, I. F. Tannock, Kimberley Reeves, Ananya Choudhury

{"title":"Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review","authors":"Hannah Louise Bromley, Mohini Varughese, Duncan C Gilbert, Peter J Hoskin, I. F. Tannock, Kimberley Reeves, Ananya Choudhury","doi":"10.1136/bmjonc-2023-000198","DOIUrl":"https://doi.org/10.1136/bmjonc-2023-000198","url":null,"abstract":"To review the efficacy and safety of low-dose versus standard-dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.Keyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide. Searches were limited to original full-text and English-language studies. Key outcomes included overall survival (OS), progression-free survival (PFS), prostate-specific antigen response and treatment-related adverse events. The review was performed in accordance with Cochrane Rapid Reviews Methods Group guidelines.Ten studies were identified that met the eligibility criteria: five phase I studies, two post-hoc analyses of phase III trials and three retrospective analyses. No consistent association between OS, PFS and drug dose was identified. Fewer severe treatment-related adverse events were observed at lower drug doses.This review provides evidence that enzalutamide, apalutamide or darolutamide could be given at a lower than the standard recommended dose without loss of antitumour activity. A prospective near-equivalence randomised trial should be undertaken to compare registered and lower doses of these agents.CRD42023440371.","PeriodicalId":505335,"journal":{"name":"BMJ Oncology","volume":"15 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140468313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0