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Laurien J. Zeverijn Eleonora J. Looze Subotheni Thavaneswaran J. Maxime van Berge Henegouwen Robert J. Simes Louisa R. Hoes Katrin M. Sjoquist Hanneke van der Wijngaart Lucille Sebastian Birgit S. Geurts Chee K. Lee Gijsbrecht F. de Wit David Espinoza Paul Roepman Frank P. Lin Anne M. L. Jansen Wendy W. J. de Leng Vincent van der Noort Lindsay V. M. Leek Filip Y. F. L. de Vos Carla M. L. van Herpen Hans Gelderblom Henk M. W. Verheul David M. Thomas Emile E. Voest 《International journal of cancer. Journal international du cancer》2023,153(7):1413-1422
The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible. 相似文献
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European Journal of Epidemiology - Existing research has found adverse short-term effects of the COVID-19 pandemic on mental health, but longer-term effects have been less documented. Using newly... 相似文献
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Zumel-Marne Angela Kundi Michael Castaño-Vinyals Gemma Alguacil Juan Petridou Eleni Th Georgakis Marios K. Morales-Suárez-Varela Maria Sadetzki Siegal Piro Sara Nagrani Rajini Filippini Graziella Hutter Hans-Peter Dikshit Rajesh Woehrer Adelheid Maule Milena Weinmann Tobias Krewski Daniel ′t Mannetje Andrea Momoli Franco Lacour Brigitte Mattioli Stefano Spinelli John J. Ritvo Paul Remen Thomas Kojimahara Noriko Eng Amanda Thurston Angela Lim Hyungryul Ha Mina Yamaguchi Naohito Mohipp Charmaine Bouka Evdoxia Eastman Chelsea Vermeulen Roel Kromhout Hans Cardis Elisabeth 《Journal of neuro-oncology》2020,147(2):427-440
Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in... 相似文献
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Renuka V. Iyer MD Bhavana Konda MD MPH Christos Fountzilas MD Sarbajit Mukherjee MD MS Dwight Owen MD MS Kristopher Attwood PhD Chong Wang MA Orla Maguire PhD Hans Minderman PhD Sheryl-Ann Suffren BA Karen Hicks BS John Wilton PhD Robert Bies PhD Danielle Casucci BA Diane Reidy-Lagunes MD Manisha Shah MD 《Cancer》2020,126(16):3689-3697
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Kristina Shkirkova Krista Lamorie-Foote Michelle Connor Arati Patel Giuseppe Barisano Hans Baertsch 《Journal of toxicology and environmental health. Part B, Critical reviews》2020,23(7):319-350
ABSTRACT Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions. 相似文献
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