دورية أكاديمية
PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.
العنوان: | PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers. |
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المؤلفون: | Dumbrava EE; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Call SG; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Huang HJ; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Stuckett AL; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Madwani K; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Adat A; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Hong DS; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Piha-Paul SA; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Subbiah V; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Karp DD; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Fu S; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Naing A; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Tsimberidou AM; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Moulder SL; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Koenig KH; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Barcenas CH; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Kee BK; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Fogelman DR; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Kopetz ES; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Meric-Bernstam F; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA., Janku F; Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: fjanku@me.com. |
المصدر: | ESMO open [ESMO Open] 2021 Oct; Vol. 6 (5), pp. 100230. Date of Electronic Publication: 2021 Aug 31. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 101690685 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2059-7029 (Electronic) Linking ISSN: 20597029 NLM ISO Abbreviation: ESMO Open Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2021 : [London] : Elsevier Original Publication: London : BMJ, [2016]- |
مواضيع طبية MeSH: | Breast Neoplasms* , Circulating Tumor DNA*/genetics, Biomarkers, Tumor/genetics ; Class I Phosphatidylinositol 3-Kinases/genetics ; Female ; Humans ; Mutation ; Phosphatidylinositol 3-Kinases/genetics ; Treatment Outcome |
مستخلص: | Background: Oncogenic mutations in PIK3CA are prevalent in diverse cancers and can be targeted with inhibitors of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Analysis of circulating tumor DNA (ctDNA) provides a minimally invasive approach to detect clinically actionable PIK3CA mutations. Patients and Methods: We analyzed PIK3CA hotspot mutation frequency by droplet digital PCR (QX 200; BioRad) using 16 ng of unamplified plasma-derived cell-free DNA from 68 patients with advanced solid tumors (breast cancer, n = 41; colorectal cancer, n = 13; other tumor types, n = 14). Results quantified as variant allele frequencies (VAFs) were compared with previous testing of archival tumor tissue and with patient outcomes. Results: Of 68 patients, 58 (85%) had PIK3CA mutations in tumor tissue and 43 (74%) PIK3CA mutations in ctDNA with an overall concordance of 72% (49/68, κ = 0.38). In a subset analysis, which excluded samples from 26 patients known not to have disease progression at the time of sample collection, we found an overall concordance of 91% (38/42; κ = 0.74). PIK3CA-mutated ctDNA VAF of ≤8.5% (5% trimmed mean) showed a longer median survival compared with patients with a higher VAF (15.9 versus 9.4 months; 95% confidence interval 6.7-17.1 months; P = 0.014). Longitudinal analysis of ctDNA in 18 patients with serial plasma collections (range 2-22 time points, median 5) showed that those with a decrease in PIK3CA VAF had a longer time to treatment failure (TTF) compared with patients with an increase or no change (10.7 versus 2.6 months; P = 0.048). Conclusions: Detection of PIK3CA mutations in ctDNA is concordant with testing of archival tumor tissue. Low quantity of PIK3CA-mutant ctDNA is associated with longer survival and a decrease in PIK3CA-mutant ctDNA on therapy is associated with longer TTF. Competing Interests: Disclosure FJ has research support from Novartis, Genentech, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, PIQUR, Symphogen, Bristol-Myers Squibb, Asana, and Upsher-Smith Laboratories; is or has been on the Scientific Advisory Boards of Guardant Health, IFM Therapeutics, Synlogic, and Deciphera; is a paid consultant for Cardiff Oncology and ImmunoMet; and has ownership interests in Cardiff Oncology. MF reports grants and personal consulting fees through 06/04/18 from Seattle Genetics and salary and stocks from 10/01/18 following the start of her employment with Seattle Genetics; grants and personal fees from Takeda, Celgene, BMS, and Merck through 06/04/18; grants from ADC Therapeutics, Molecular Templates, MedImmune, Gilead, and Genentech through 06/04/18; and personal fees from Bayer and Spectrum through 06/04/18. VS has research funding/grant support for clinical trials (to institution) from Novartis, Bayer, Berghealth, Incyte, Fujifilm, PharmaMar, D3, Pfizer, MultiVir, Amgen, AbbVie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Loxo Oncology, MedImmune, Altum, Dragonfly Therapeutics, Takeda and, National Comprehensive Cancer Network, NCI-CTEP, UT MD Anderson Cancer Center, Turning point therapeutics, and Boston Pharmaceuticals; travel funding from Novartis, PharmaMar, ASCO, ESMO, Helsinn, Incyte; and serves on the advisory board of Helsinn, LOXO Oncology/ Eli Lilly, R-Pharma US, INCYTE, QED pharma, Astra-Zeneca/Medimmune, Novartis, Signant Health. The remaining authors have declared no conflicts of interest. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
References: | Clin Cancer Res. 2017 Sep 15;23(18):5648-5656. (PMID: 28536309) Cancer Discov. 2021 Jan;11(1):92-107. (PMID: 32958578) Nat Rev Cancer. 2002 Jul;2(7):489-501. (PMID: 12094235) Oncogene. 2008 Sep 18;27(41):5497-510. (PMID: 18794884) Nat Med. 2017 Jun;23(6):703-713. (PMID: 28481359) Clin Cancer Res. 2016 Nov 15;22(22):5497-5505. (PMID: 27185373) Cell Rep. 2014 Jan 30;6(2):377-87. (PMID: 24440717) Science. 2004 Apr 23;304(5670):554. (PMID: 15016963) Cancer Res. 2013 Jan 1;73(1):276-84. (PMID: 23066039) J Clin Oncol. 2018 May 1;36(13):1291-1299. (PMID: 29401002) Sci Transl Med. 2011 Mar 23;3(75):75ra26. (PMID: 21430269) Clin Cancer Res. 2020 Apr 15;26(8):1924-1931. (PMID: 31852833) Nat Rev Drug Discov. 2014 Feb;13(2):140-56. (PMID: 24481312) Ann Oncol. 2010 Feb;21(2):255-262. (PMID: 19633047) Ann Oncol. 2017 Jun 1;28(6):1294-1301. (PMID: 28368441) Expert Rev Mol Diagn. 2015;15(12):1631-44. (PMID: 26559503) Nat Rev Drug Discov. 2009 Aug;8(8):627-44. (PMID: 19644473) Clin Cancer Res. 2017 Jul 15;23(14):3657-3666. (PMID: 28096270) Cancer Discov. 2020 Dec;10(12):1842-1853. (PMID: 32816849) Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774) Annu Rev Pathol. 2009;4:127-50. (PMID: 18767981) Oncotarget. 2015 May 20;6(14):12809-21. (PMID: 25980577) Biochem Med (Zagreb). 2012;22(3):276-82. (PMID: 23092060) N Engl J Med. 2019 May 16;380(20):1929-1940. (PMID: 31091374) Curr Top Microbiol Immunol. 2010;347:21-41. (PMID: 20535651) Nat Cancer. 2020 Apr;1(4):382-393. (PMID: 32864625) JAMA Oncol. 2019 Feb 1;5(2):e184475. (PMID: 30543347) Ann Oncol. 2017 Mar 1;28(3):642-650. (PMID: 27993791) J Clin Oncol. 2012 Mar 10;30(8):777-82. (PMID: 22271473) Mol Cancer Ther. 2016 Jun;15(6):1397-404. (PMID: 27207774) Mol Cancer Ther. 2011 Mar;10(3):558-65. (PMID: 21216929) Sci Transl Med. 2014 Feb 19;6(224):224ra24. (PMID: 24553385) Clin Cancer Res. 2012 Jun 15;18(12):3462-9. (PMID: 22421194) Br J Cancer. 2006 Feb 27;94(4):455-9. (PMID: 16449998) Nat Rev Clin Oncol. 2018 May;15(5):273-291. (PMID: 29508857) Lancet Oncol. 2017 Jul;18(7):904-916. (PMID: 28576675) Fam Med. 2005 May;37(5):360-3. (PMID: 15883903) Nat Med. 2008 Dec;14(12):1351-6. (PMID: 19029981) |
معلومات مُعتمدة: | K12 CA088084 United States CA NCI NIH HHS; P30 CA016672 United States CA NCI NIH HHS; UL1 TR000371 United States TR NCATS NIH HHS; UL1 TR003167 United States TR NCATS NIH HHS |
فهرسة مساهمة: | Keywords: PIK3CA; cancer; circulating tumor DNA; droplet digital PCR |
المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Circulating Tumor DNA) EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) EC 2.7.1.137 (PIK3CA protein, human) |
تواريخ الأحداث: | Date Created: 20210903 Date Completed: 20211029 Latest Revision: 20220531 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC8414046 |
DOI: | 10.1016/j.esmoop.2021.100230 |
PMID: | 34479035 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2059-7029 |
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DOI: | 10.1016/j.esmoop.2021.100230 |