160 CHAPTER 6 reported that 22.4% of patients had a PFS2/PFS1 ratio of ≥ 1.5, and thereby failed to meet its pre-specified primary end point12. Despite its negative outcome, the WINTHER trial reports that transcriptome analysis of tumor tissue added substantially to the number of patients treated with a matched targeted drug. By using information from RNA analysis, the matching rate improved from 23% to 35%12. The addition of RNA sequencing and transcriptome-based treatment selection is also considered as a new strategy within DRUP. One of the factors contributing to the meaningful clinical benefit rate in the DRUP trial may be the innovative trial design, which allows evaluation of small groups of patients with rare cancer subtypes to determine the potential benefit of a targeted agent in a group of patients with a specific tumor molecular profile while appreciating the context of histology. DRUP has a wide arsenal of available targeted drugs, with 30 treatments currently available provided through collaboration with 12 pharmaceutical companies, and efforts to further expand are ongoing. A dedicated team of researchers evaluate each case, and alongside the molecular target evaluation, a literature search is performed to appreciate existing (pre-)clinical evidence for the drug-target-histology combination, which substantially impacts the choice of therapy. Another contributing factor may be the increasingly broad molecular testing that is performed in the Netherlands. Since the molecular diagnostic approach is the corner stone of precision oncology, an improvement to the design of DRUP could be to include molecular profiling for target identification on fresh frozen biopsies in the trial. Several other trials have broad-panel sequencing or transcriptome analysis as “prescreening” in their trial design, for example the I-PREDICT13 and NCI-MATCH14 trials. In the latter, patients’ tumor tissue was screened for actionable genomic targets by NGS and matched to a targeted treatment accordingly. Although the NGS results contributed to the knowledge on actionability of genomic events, only a minority of included patients experienced clinical benefit upon targeted treatment15. As in DRUP, clinical benefit rates differed greatly among various cohorts and targeted pathways. One of the challenges in many precision-oncology clinical trials is how to generate a sufficient level of evidence for the (lack of) effectivity of a drug in very rare subgroups of cancer patients. Some actionable genomic events occur in such low frequency that timely completion of a DRUP cohort and reporting of the results is considered impossible. One solution to this problem requires international collaboration of data sharing with other research groups and participation in collaborative clinical trials. DRUP has formed a global collaboration with two other trial-groups by harmonizing the study protocols: the United States-based Targeted Agent and Profiling Utilization Registry (TAPUR) Study (NCT02693535)16 and the Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR, NCT03297606). This collaboration comprises a data sharing protocol that allows pooling and combined analysis of comparable cohorts across the three trials17. As time went on, it became clear that other European countries and research groups also had an interest in starting similar precision oncology trials. Working towards a European precision oncology platform. Therefore, DRUP has also shared its protocol and study documents with these European groups to harmonize protocols and facilitate data sharing closer to home. At the time of writing, several trials have already started enrolling
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