دورية أكاديمية
أعرض في EDS

Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.

التفاصيل البيبلوغرافية
العنوان: Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.
المؤلفون: Martin-Broto J; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain. jmartin@atbsarc.org.; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, 28040, Madrid, Spain. jmartin@atbsarc.org.; General de Villalba University Hospital, 28400, Madrid, Spain. jmartin@atbsarc.org., Martinez-Garcia J; Medical Oncology Department, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain., Moura DS; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain., Redondo A; Department of Medical Oncology, Hospital Universitario La Paz-IdiPAZ, P. Castellana, 261, 28046, Madrid, Spain., Gutierrez A; Hematology Department, University Hospital Son Espases, 07120, Mallorca, Spain., Lopez-Pousa A; Medical Oncology Department, Sant Pau Hospital, 08025, Barcelona, Spain., Martinez-Trufero J; Medical Oncology Department, University Hospital Miguel Servet, 50009, Zaragoza, Spain., Sevilla I; Investigación Clínica y Traslacional en Cáncer/ Instituto de Investigaciones Biomédicas de Malaga (IBIMA)/ Hospitales Universitarios Regional y Virgen de la Victoria de Malaga, Malaga, Spain., Diaz-Beveridge R; Medical Oncology Department, Hospital Universitari i Politècnic La Fe, 46026, Valencia, Spain., Solis-Hernandez MP; Medical Oncology Department, Central University Hospital of Asturias, 33011, Oviedo, Spain., Carnero A; Instituto de Biomedicina de Sevilla (IBiS; HUVR, CSIC, US), 41013, Sevilla, Spain., Perez M; Instituto de Biomedicina de Sevilla (IBiS; HUVR, CSIC, US), 41013, Sevilla, Spain.; Pathology Department, Virgen del Rocio University Hospital, 41013, Sevilla, Spain., Marcilla D; Pathology Department, Virgen del Rocio University Hospital, 41013, Sevilla, Spain., Garcia-Foncillas J; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain.; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, 28040, Madrid, Spain., Romero P; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain., Fernandez-Jara J; Radiology Department, Fundación Jimenez Diaz University Hospital, 28040, Madrid, Spain., Lopez-Lopez D; Instituto de Biomedicina de Sevilla (IBiS; HUVR, CSIC, US), 41013, Sevilla, Spain.; Computational Medicine Platform, Fundación progreso y salud (FPS), Hospital Virgen del Rocío, 41013, Seville, Spain.; Bioinformatics in Rare Diseases (BiER). Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), FPS, Hospital Virgen del Rocio, Sevilla, Spain., Arribas I; Universitat de València - ERI-CES, 46010, Valencia, Spain., Hindi N; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain.; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, 28040, Madrid, Spain.; General de Villalba University Hospital, 28400, Madrid, Spain.
المصدر: Signal transduction and targeted therapy [Signal Transduct Target Ther] 2023 Oct 25; Vol. 8 (1), pp. 405. Date of Electronic Publication: 2023 Oct 25.
نوع المنشور: Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101676423 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-3635 (Electronic) Linking ISSN: 20593635 NLM ISO Abbreviation: Signal Transduct Target Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Publishing Group, [2016]-
مواضيع طبية MeSH: Lipopolysaccharides* , Sarcoma*/genetics, Adult ; Humans ; Piperazines/therapeutic use ; Piperazines/pharmacology ; RNA, Messenger ; Cyclin-Dependent Kinase 4/genetics ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism
مستخلص: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas. Advanced adult-type soft-tissue sarcoma, excluding DD-LPS, or bone sarcoma patients, progressing after at least one systemic line, whose tumors overexpressed CDK4, but not CDKN2A at baseline biopsy, were accrued in this single-arm phase II trial (EudraCT number: 2016-004039-19). With the main endpoint of a 6-month PFS rate, 40% was considered promising in this population. Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles. A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening, archival material (141), and screening, baseline biopsy (95). There were 28 (29%) with favorable mRNA profiles from 95 screened patients at baseline. From 23 enrolled patients, 21 evaluable, the 6-month PFS rate was 29% (95% CI 9-48), and there were 6 patients out of 21 with a PFS longer than 6 months. The median PFS and overall survival were 4.2 (95% CI 3.6-4.8) and 12 (95% CI 8.7-15.4) months, respectively. Translational research showed a significant correlation between CDK4 mRNA and protein expression. Palbociclib was active in a variety of sarcoma subtypes, selected by CDK4/CDKN2A, and deserves further investigation in the sarcoma context.
(© 2023. West China Hospital, Sichuan University.)
References: Cancer Res. 2002 Nov 1;62(21):6240-5. (PMID: 12414653)
Ann Oncol. 2017 Dec 01;28(12):2994-2999. (PMID: 29045512)
N Engl J Med. 2010 Oct 28;363(18):1727-33. (PMID: 20979472)
Cell. 2017 Nov 2;171(4):950-965.e28. (PMID: 29100075)
Eur J Cancer. 2002 Mar;38(4):543-9. (PMID: 11872347)
Lancet Oncol. 2017 Aug;18(8):1089-1103. (PMID: 28651927)
Lancet. 2012 May 19;379(9829):1879-86. (PMID: 22595799)
J Clin Oncol. 2016 Mar 10;34(8):786-93. (PMID: 26371143)
Oncotarget. 2015 Dec 1;6(38):40557-74. (PMID: 26528855)
BMC Med. 2017 Apr 10;15(1):78. (PMID: 28391775)
Nucleic Acids Res. 2019 Jan 8;47(D1):D941-D947. (PMID: 30371878)
JAMA. 2020 Apr 7;323(13):1266-1276. (PMID: 32259228)
Lancet Oncol. 2019 Jun;20(6):837-848. (PMID: 31078463)
Cancer Discov. 2017 Aug;7(8):818-831. (PMID: 28572459)
J Clin Oncol. 2013 Jun 1;31(16):2024-8. (PMID: 23569312)
Lancet Oncol. 2019 Jan;20(1):134-144. (PMID: 30578023)
Neuro Oncol. 2012 Jul;14(7):870-81. (PMID: 22711607)
Breast Cancer Res. 2009;11(5):R77. (PMID: 19874578)
J Carcinog. 2016 May 20;15:3. (PMID: 27298590)
Clin Cancer Res. 2020 Jun 15;26(12):2997-3011. (PMID: 32086342)
Clin Cancer Res. 2020 Jul 15;26(14):3881-3888. (PMID: 32299819)
JCO Precis Oncol. 2022 Feb;6:e2100211. (PMID: 35108033)
Hum Pathol. 2017 Sep;67:1-10. (PMID: 28551330)
Lancet Oncol. 2019 Sep;20(9):1252-1262. (PMID: 31331701)
Lancet Oncol. 2015 Jan;16(1):25-35. (PMID: 25524798)
Clin Sarcoma Res. 2019 Sep 11;9:12. (PMID: 31528332)
Ann Oncol. 2010 May;21(5):1135-7. (PMID: 20215136)
Diagn Mol Pathol. 1996 Mar;5(1):65-73. (PMID: 8919547)
Lancet Oncol. 2015 Jan;16(1):98-107. (PMID: 25498219)
Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
Trends Cancer. 2017 Jan;3(1):39-55. (PMID: 28303264)
Cancer. 2016 Jan 1;122(1):17-9. (PMID: 26479175)
Sarcoma. 2019 Jan 21;2019:3914232. (PMID: 30804704)
Anticancer Res. 2019 Aug;39(8):4079-4084. (PMID: 31366491)
Cancer Cell. 2017 Dec 11;32(6):761-776.e6. (PMID: 29232554)
Cell Death Dis. 2018 Apr 18;9(5):446. (PMID: 29670090)
J Adolesc Young Adult Oncol. 2020 Dec;9(6):628-638. (PMID: 32379517)
Anticancer Res. 2021 Jul;41(7):3287-3292. (PMID: 34230123)
Cancer Res. 2016 May 15;76(10):2990-3002. (PMID: 26988987)
Lancet Oncol. 2021 Sep;22(9):1312-1321. (PMID: 34416158)
Nucleic Acids Res. 2021 Jul 2;49(W1):W21-W28. (PMID: 34023905)
Lancet Oncol. 2019 Jul;20(7):1023-1034. (PMID: 31160249)
JAMA Oncol. 2016 Jul 1;2(7):937-40. (PMID: 27124835)
Mol Cancer Ther. 2004 Nov;3(11):1427-38. (PMID: 15542782)
Lancet. 2016 Apr 16;387(10028):1629-37. (PMID: 26874885)
Lancet Oncol. 2020 Mar;21(3):456-466. (PMID: 32066540)
Bioinformatics. 2018 Oct 15;34(20):3572-3574. (PMID: 29669011)
Sci Rep. 2015 May 06;5:10120. (PMID: 25944566)
معلومات مُعتمدة: 29363 United Kingdom CRUK_ Cancer Research UK; C56167/A29363 United Kingdom CRUK_ Cancer Research UK
المشرفين على المادة: G9ZF61LE7G (palbociclib)
0 (Lipopolysaccharides)
0 (Piperazines)
0 (RNA, Messenger)
EC 2.7.11.22 (CDK4 protein, human)
EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
0 (CDKN2A protein, human)
0 (Cyclin-Dependent Kinase Inhibitor p16)
تواريخ الأحداث: Date Created: 20231024 Date Completed: 20231027 Latest Revision: 20240306
رمز التحديث: 20240306
مُعرف محوري في PubMed: PMC10598203
DOI: 10.1038/s41392-023-01661-8
PMID: 37875500
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-3635
DOI:10.1038/s41392-023-01661-8