دورية أكاديمية
أعرض في EDS

PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.

التفاصيل البيبلوغرافية
العنوان: PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.
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.)
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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
الوصف
تدمد:2059-7029
DOI:10.1016/j.esmoop.2021.100230