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The NCI-MATCH trial and precision medicine in gynecologic cancers

Published:January 21, 2018DOI:https://doi.org/10.1016/j.ygyno.2018.01.008

      Highlights

      • Overview of the NCI-MATCH trial.
      • Key concepts surrounding molecular genomics and cancer therapies.
      • Update on FDA approved precision therapies available for gynecologic cancers.

      Abstract

      The Precision Medicine Initiative is a National Cancer Institute (NCI) driven interdisciplinary collaborative effort to test the feasibility of trials incorporating genomic profiling when choosing patient therapies. The goal of the initiative is to generate the scientific evidence needed to move the concept of precision medicine, or targeted therapy, into clinical practice. The rapid development and widespread availability of next generation sequencing provides access to information regarding an individual's tumor at various times during the course of their disease. Translating the aberrations specific to a patient's tumor into personalized treatment is the concept behind “basket” trials, and thus categorize patients' cancers based on the sequencing of the tumor, rather than the organ of origin. The NCI Molecular Analysis for Therapy Choice (MATCH) trial [NCT02465060] is a multi-site, collaborative effort between the NCI and several pharmaceutical companies that is beginning to clarify the significance of molecular alterations in tumors. This trial was designed to assign targeted treatment based on molecular alterations identified from a tumor biopsy obtained after study enrollment and determine the efficacy of this treatment. This review article will briefly discuss known genomic aberrations in gynecologic cancers, and then provide an overview of the NCI-MATCH trial with an update on accrual and recent interim analysis. We will also review current FDA-approved precision therapies for gynecologic malignancies, such as poly (ADP ribose) polymerase (PARP) inhibitors.

      Keywords

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      References

        • Collins F.S.
        • V.H.
        A new initiative on precision medicine.
        N. Engl. J. Med. 2015; 372: 793-795
        • Coyne G.O.
        • Takebe N.
        • Chen A.P.
        Defining precision: the precision medicine initiative trials NCI-MPACT and NCI-MATCH.
        Curr. Probl. Cancer. 2017; 41: 182-193
        • Xuan J.
        • et al.
        Next-generation sequencing in the clinic: promises and challenges.
        Cancer Lett. 2013; 340: 284-295
      1. Nature. 2011; 474: 609-615
        • Berns E.M.
        • Bowtell D.D.
        The changing view of high-grade serous ovarian cancer.
        Cancer Res. 2012; 72: 2701-2704
        • Liu J.
        • Matulonis U.A.
        New strategies in ovarian cancer: translating the molecular complexity of ovarian cancer into treatment advances.
        Clin. Cancer Res. 2014; 20: 5150-5156
        • Tothill R.W.
        • et al.
        Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
        Clin. Cancer Res. 2008; 14: 5198-5208
        • Patch A.M.
        • et al.
        Whole-genome characterization of chemoresistant ovarian cancer.
        Nature. 2015; 521: 489-494
        • Wong K.K.
        • et al.
        BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas.
        Am. J. Pathol. 2010; 177: 1611-1617
        • Emmanuel C.
        • et al.
        Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.
        Clin. Cancer Res. 2014; 20: 6618-6630
        • Hunter S.M.
        • et al.
        Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.
        Oncotarget. 2015; 6: 37663-37677
        • Kandoth C.
        • et al.
        Integrated genomic characterization of endometrial carcinoma.
        Nature. 2013; 497: 67-73
        • Depreeuw J.
        • et al.
        Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies.
        Gynecol. Oncol. 2015; 139: 118-126
        • Wang Y.
        • et al.
        Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways.
        Gynecol. Oncol. 2016; 143: 168-178
        • Oda K.
        • et al.
        Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies.
        J. Obstet. Gynaecol. Res. 2016; 42: 757-762
        • DeLair D.F.
        • et al.
        The genetic landscape of endometrial clear cell carcinomas.
        J. Pathol. 2017; 243: 230-241
        • Wright A.A.
        • et al.
        Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix.
        Cancer. 2013; 119: 3776-3783
        • Do K.
        • O.S.C.G.
        • Chen P.
        An overview of the NCI precision medicine trials-NCI Match and MPACT.
        Chin. Clin. Oncol. 2015; 4: 31
        • Flaherty K.T.
        • Chen A.P.
        • O'Dwyer P.J.
        • Conley B.A.
        • Hamilton S.R.
        • Williams M.
        • Gray R.J.
        • Li S.
        • McShane L.M.
        • Rubinstein L.V.
        • Lee S.I.
        • Lin F.I.
        • Caimi P.F.
        • Nemcek Jr., A.A.
        • Mitchell E.P.
        • Zwiebel J.A.
        NCI-Molecular analysis for therapy choice (NCI-MATCH or EAY131).
        Natl. Cancer Inst. 2016; : 1-27
        • Afghahi A.
        • et al.
        Tumor BRCA1 reversion mutation arising during neoadjuvant platinum-based chemotherapy in triple-negative breast cancer is associated with therapy resistance.
        Clin. Cancer Res. 2017; 23: 3365-3370
        • Hanahan D.
        • Weinberg R.A.
        Hallmarks of cancer: the next generation.
        Cell. 2011; 144: 646-674
        • Zhu P.
        • et al.
        Expression of VEGF and HIF-1alpha in locally advanced cervical cancer: potential biomarkers for predicting preoperative radiochemotherapy sensitivity and prognosis.
        Onco Targets Ther. 2016; 9: 3031-3037
        • Burger R.A.
        • et al.
        Incorporation of bevacizumab in the primary treatment of ovarian cancer.
        N. Engl. J. Med. 2011; 365: 2473-2483
        • Perren T.J.
        • et al.
        A phase 3 trial of bevacizumab in ovarian cancer.
        N. Engl. J. Med. 2011; 365: 2484-2496
        • Aghajanian C.
        • et al.
        OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.
        J. Clin. Oncol. 2012; 30: 2039-2045
        • Aghajanian C.
        • et al.
        Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer.
        Gynecol. Oncol. 2015; 139: 10-16
        • Pujade-Lauraine E.
        • et al.
        Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial.
        J. Clin. Oncol. 2014; 32: 1302-1308
        • Coleman R.L.
        • et al.
        Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG oncology/gynecologic oncology group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial.
        Lancet Oncol. 2017; 18: 779-791
        • Tewari K.S.
        • et al.
        Improved survival with bevacizumab in advanced cervical cancer.
        N. Engl. J. Med. 2014; 370: 734-743
        • Orbegoso C.
        • et al.
        The role of Cediranib in ovarian cancer.
        Expert. Opin. Pharmacother. 2017; 18: 1637-1648
        • Ntanasis-Stathopoulos I.
        • et al.
        The emerging role of tyrosine kinase inhibitors in ovarian cancer treatment: a systematic review.
        Cancer Investig. 2016; 34: 313-339
        • Ledermann J.A.
        • et al.
        Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.
        Lancet. 2016; 387: 1066-1074
        • Bender D.
        • et al.
        A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: an NRG oncology/gynecologic oncology group study.
        Gynecol. Oncol. 2015; 138: 507-512
        • Ame J.C.
        • Spenlehauer C.
        • de Murcia G.
        The PARP superfamily.
        BioEssays. 2004; 26: 882-893
        • Helleday T.
        The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings.
        Mol. Oncol. 2011; 5: 387-393
        • Murai J.
        • et al.
        Trapping of PARP1 and PARP2 by clinical PARP inhibitors.
        Cancer Res. 2012; 72: 5588-5599
        • Domchek S.M.
        • et al.
        Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy.
        Gynecol. Oncol. 2016; 140: 199-203
        • Pujade-Lauraine E.
        • et al.
        Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2017; 18: 1274-1284
        • Kaufman B.
        • et al.
        Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.
        J. Clin. Oncol. 2015; 33: 244-250
        • Lee L.
        • Gupta M.
        • Sahasranaman S.
        Immune checkpoint inhibitors: an introduction to the next-generation cancer immunotherapy.
        J. Clin. Pharmacol. 2016; 56: 157-169
        • Le D.T.
        • D.J.
        • Smith K.N.
        • et al.
        Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade.
        Science. 2017; 357: 409-413
        • Ott P.A.
        • et al.
        Safety and antitumor activity of Pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study.
        J. Clin. Oncol. 2017; 35: 2535-2541
        • Swanton C.
        Intratumor heterogeneity: evolution through space and time.
        Cancer Res. 2012; 72: 4875-4882
        • Gerlinger M.
        • et al.
        Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
        N. Engl. J. Med. 2012; 366: 883-892
        • Catenacci D.V.
        Next-generation clinical trials: novel strategies to address the challenge of tumor molecular heterogeneity.
        Mol. Oncol. 2015; 9: 967-996
        • Bashashati A.
        • et al.
        Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling.
        J. Pathol. 2013; 231: 21-34
        • Tannock I.F.
        • Hickman J.A.
        Limits to personalized cancer medicine.
        N. Engl. J. Med. 2016; 375: 1289-1294
        • Prasad V.
        Perspective: the precision-oncology illusion.
        Nature. 2016; 537: S63