A Long Way to Go: A Scenario for Clinical Trials of PI3K Inhibitors in Treating Cancer.

IF 2.5 4区 医学 Q3 ONCOLOGY Cancer Control Pub Date : 2024-01-01 DOI:10.1177/10732748241238047
Bárbara Adriana Ferreira Dos Santos Trigueiros, Ivan José Santana Santos, Fabricia Pires Pimenta, Andréa Rodrigues Ávila
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Abstract

Background: Alterations in PI3K function are directly related to cancer, making PI3K inhibitors suitable options for anticancer therapies. Information on therapy using different types of PI3K inhibitors is available in literature, providing indications of trends in developing new therapies. Although some studies on PI3K inhibitors for cancer treatment provide clinical evidence, they do not allow a careful search for potential PI3K inhibitors conducted by development indicators. Here, we performed a foresight study of clinical trials involving PI3K inhibitors from the past 11 years using indicators of clinical evolution to identify technological trends and provide data for supporting recommendations for new study designs.

Methods: A comprehensive foresight study was designed based on documents from clinical trials on PI3K inhibitors to perform a systematic and comparative analysis, in order to identify technological trends on new cancer therapies.

Results: Our results demonstrate that total number of clinical trials has decreased over the years and, currently, there is a clear prevalence of studies using isoform-specific inhibitors in combined interventions. Clinical trials in Phases I and II were the most frequently found in the database, whereas Phase III trials correspond to 7% of studies. The measurement of clinical trials progression using indicators (drugs in Phase III profile, top-10 drugs, and top-10 combined drugs) demonstrated that the 3 new medicines BKM120, IBI-376, and PF-05212384 have a high potential to provide more efficient cancer treatment in combined interventions. These data also include the groups of targets for each drug, providing a useful and reliable source for design new combinations to overcome the resistance and the poor tolerability observed in some PI3K therapies.

Conclusions: The establishment of development indicators based on clinical trials for cancer treatment was useful to highlight the clinical investment in 3 new PI3K drugs and the advantages of combine therapy using FDA-approved drugs.

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任重道远:PI3K抑制剂治疗癌症的临床试验前景。
背景:PI3K 功能的改变与癌症直接相关,因此 PI3K 抑制剂是抗癌疗法的合适选择。有关使用不同类型 PI3K 抑制剂进行治疗的信息见诸文献,为开发新疗法提供了趋势指示。虽然一些关于 PI3K 抑制剂治疗癌症的研究提供了临床证据,但这些研究并不能根据开发指标仔细寻找潜在的 PI3K 抑制剂。在此,我们利用临床演变指标对过去 11 年涉及 PI3K 抑制剂的临床试验进行了前瞻性研究,以确定技术趋势,并为新的研究设计建议提供数据支持:根据PI3K抑制剂临床试验的文件设计了一项全面的前瞻性研究,以进行系统的比较分析,从而确定癌症新疗法的技术趋势:我们的研究结果表明,临床试验的总数逐年减少,目前在联合干预中使用同工酶特异性抑制剂的研究明显增多。数据库中I期和II期临床试验最多,而III期临床试验只占7%。利用指标(Ⅲ期临床试验中的药物、排名前十的药物和排名前十的联合用药)对临床试验进展的衡量表明,BKM120、IBI-376 和 PF-05212384 这三种新药在联合干预中提供更有效癌症治疗的潜力很大。这些数据还包括每种药物的靶点群,为设计新的联合疗法提供了有用而可靠的依据,以克服在某些 PI3K 疗法中观察到的耐药性和耐受性差的问题:基于癌症治疗临床试验的发展指标的建立有助于突出 3 种 PI3K 新药的临床投资以及使用 FDA 批准药物进行联合治疗的优势。
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来源期刊
Cancer Control
Cancer Control ONCOLOGY-
CiteScore
3.80
自引率
0.00%
发文量
148
审稿时长
>12 weeks
期刊介绍: Cancer Control is a JCR-ranked, peer-reviewed open access journal whose mission is to advance the prevention, detection, diagnosis, treatment, and palliative care of cancer by enabling researchers, doctors, policymakers, and other healthcare professionals to freely share research along the cancer control continuum. Our vision is a world where gold-standard cancer care is the norm, not the exception.
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