New clinical trial designs in the era of precision medicine

Garralda, Elena; Dienstmann, Rodrigo; Piris-Giménez, Alejandro; Braña, Irene; Rodón, Jordi; Tabernero, Josep

doi:10.1002/1878-0261.12465

Cited by 92 publications

(88 citation statements)

References 38 publications

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“…CIViC database [78,149] OncoKB database [77,150] Standards and guidelines for the interpretation and reporting of sequence variants in cancer [86] MAP [163,164]. A number of basket trials around the world are currently recruiting patients, some of which are highlighted in Table 4.…”

Section: Variantmentioning

confidence: 99%

Molecular profiling for precision cancer therapies

et al. 2020

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The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types. Molecular pathology has therefore become fundamental not only to inform on tumor diagnosis and prognosis but also to drive therapeutic decisions in daily practice. The introduction of next-generation sequencing technologies and the rising number of large-scale tumor molecular profiling programs across institutions worldwide have revolutionized the field of precision oncology. As comprehensive genomic analyses become increasingly available in both clinical and research settings, healthcare professionals are faced with the complex tasks of result interpretation and translation. This review summarizes the current and upcoming approaches to implement precision cancer medicine, highlighting the challenges and potential solutions to facilitate the interpretation and to maximize the clinical utility of molecular profiling results. We describe novel molecular characterization strategies beyond tumor DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analyses. We also review current and potential applications of liquid biopsies to evaluate blood-based biomarkers, such as circulating tumor cells and circulating nucleic acids. Last, lessons learned from the existing limitations of genotype-derived therapies provide insights into ways to expand precision medicine beyond genomics.

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Section: Variantmentioning

confidence: 99%

Molecular profiling for precision cancer therapies

et al. 2020

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“…Identifying those molecular features has led to a clinical strategy in which testing upfront or after first-line failure may provide certain novel therapeutic opportunities. In umbrella trials, patients diagnosed with the same type of solid tumors are treated according to their molecular features, while in basket trials, patients diagnosed with different types of solid tumors with a common driver molecular alteration are selected and treated with a specific inhibitor [36]. As an example, a multisite study (including >1000 patients with non-small cell lung cancer) showed that matching was associated with longer survival than was seen in patients without genotype-directed treatment.…”

Section: The Revolution Of Tumor Treatment: From Tumor Site To Molecumentioning

confidence: 99%

Personalized Medicine: Recent Progress in Cancer Therapy

Gambardella

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et al. 2020

Cancers

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Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. Nonetheless, some weaknesses need to be addressed. The complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. In light of this, there is growing interest in the role of multidisciplinary committees or molecular tumor boards to try to enhance selection. The aim of this review is to critically analyze the evolution of cancer treatment towards a precision approach, underlining some recent successes and unexpected failures.

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“…commercial/financial consequences [2]. An evolution has started towards more innovative, efficient and adaptive trial designs [39], built around active participation of patients and patient organisations. Adaptive clinical trials, irrespective of the trial phase, use the results accumulated in the trial to modify the trial's course in accordance with pre-specified rules [40].…”

Section: … To Innovation In Regulation and Businessmentioning

confidence: 99%