1,249
Views
34
CrossRef citations to date
0
Altmetric
Drug Evaluation

Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer

, , , &
Pages 597-611 | Received 23 Oct 2015, Accepted 17 Feb 2016, Published online: 16 Mar 2016

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan;66(1):7–30.
  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225–249.
  • Korkmaz T, Seber S, Basaran G. Review of the current role of targeted therapies as maintenance therapies in first and second line treatment of epithelial ovarian cancer; In the light of completed trials. Crit Rev Oncol Hematol. 2016 Feb;98:180–188.
  • Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nature Reviews Cancer. 2012 Dec;12(12):801–817.
  • Friedberg EC, Walker GC, Siede W, et al. DNA repair and mutagenesis. Second. Washington, DC: ASM Press; 2006.
  • Glazer PM, Hegan DC, Lu Y, et al. Hypoxia and DNA repair. Yale J Biol Med. 2013 Dec;86(4):443–451.
  • Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, et al. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem. 2004;73:39–85.
  • Wood RD, Mitchell M, Sgouros J, et al. Human DNA repair genes. Science 2001 Feb 16;291(5507):1284–1289.
  • Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001 May 17;411(6835):366–374.
  • Morgan MA, Parsels LA, Maybaum J, et al. Improving the efficacy of chemoradiation with targeted agents. Cancer Discov. 2014 Mar;4(3):280–291.
  • Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research. 2002 Jul;8(7):2286–2291.
  • Meng AX, Jalali F, Cuddihy A, et al. Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncology: Journal Eur Soc Ther Radiol Oncol. 2005 Aug;76(2):168–176.
  • Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005 Apr 14;434(7035):913–917.
  • De Soto JA, Wang X, Tominaga Y, et al. The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors. Int J Biol Sci. 2006;2(4):179–185.
  • Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917–921.
  • Nguewa PA, Fuertes MA, Cepeda V, et al. Poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide enhances apoptosis induction by platinum complexes in cisplatin-resistant tumor cells. Med Chem. 2006 Jan;2(1):47–53.
  • Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003 May;72(5):1117–1130.
  • King M-C, Marks JH, Mandell JB, et al. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003 Oct 24;302(5645):643–646.
  • Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 30;474(7353):609–615.
  • Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18032–18037.
  • Drew Y, Mulligan EA, Vong W-T, et al. Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2. J Natl Cancer Inst. 2011 Feb 16;103(4):334–346.
  • Patel AG, Sarkaria JN, Kaufmann SH. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci U S A. 2011;108(8):3406–3411.
  • Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245–251.
  • Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009 Jul 9;361(2):123–134.
  • Fong PC, Yap TA, Boss DS, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol. 2010;28(15):2512–2519.
  • Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852–861.
  • Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235–244.
  • Murai J, Pommier Y. PARP inhibitors for cancer therapy. Cham: Springer International; 2015.
  • Investigator’s Brochure for Olaparib, Polyadenosine 5ʹ-diphosphoribose polymerase (PARP) inhibitor (AZD2281, KU-0059436), Ed. 12. AstraZeneca Corp. June 29, 2015.
  • Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852–861.
  • Kassis JN, Cohen JG, Rasool N, et al. Models for Angiogenesis. The Cancer Handbook. 2007.
  • Hollingsworth HC, Kohn EC, Steinberg SM, et al. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol. 1995 Jul;147(1):33–41.
  • Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995 May;146(5):1029–1039.
  • Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985.
  • Forsythe JA, Jiang BH, Iyer NV, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996 Sep;16(9):4604–4613.
  • Hirte H, Lheureux S, Fleming GF, et al. A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the princess margaret, Chicago and California Phase II consortia. Gynecol Oncol. 2015;138(1):55–61.
  • Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clinical Oncology: Official Journal Am Soc Clin Oncol. 2009 Nov 20;27(33):5601–5606.
  • Matei D, Sill MW, Lankes HA, et al. Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. J Clinical Oncology: Official Journal Am Soc Clin Oncol. 2011 Jan 1;29(1):69–75.
  • Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research. 2003 Jan;9(1):327–337.
  • Pujade-Lauraine E, Hilpert F, Weber B, 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(13):1302–1308.
  • Liu JF, Tolaney SM, Birrer M, et al. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013;49(14):2972–2978.
  • Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15(11):1207–1214.
  • Jayson GC, Kohn EC, Kitchener HC, et al. Ovarian cancer. Lancet 2014 Oct 11;384(9951):1376–1388.
  • Du Bois A, Floquet A, Kim J-W, et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clinical Oncology: Official Journal Am Soc Clin Oncol. 2014 Oct 20;32(30):3374–3382.
  • Ivy SP, Wick JY, Kaufman BM. An overview of small-molecule inhibitors of VEGFR signaling. Nat Reviews Clin Oncology. 2009 Oct;6(10):569–579.
  • Brave SR, Ratcliffe K, Wilson Z, et al. Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol Cancer Ther. 2011 May;10(5):861–873.
  • Heckman CA, Holopainen T, Wirzenius M, et al. The tyrosine kinase inhibitor cediranib blocks ligand-induced vascular endothelial growth factor receptor-3 activity and lymphangiogenesis. Cancer Res. 2008 Jun 15;68(12):4754–4762.
  • Smith NR, James NH, Oakley I, et al. Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts. Mol Cancer Ther. 2007 Aug;6(8):2198–2208.
  • Wedge SR, Kendrew J, Hennequin LF, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389–4400.
  • Decio A, Cesca M, Bizzaro F, et al. Cediranib combined with chemotherapy reduces tumor dissemination and prolongs the survival of mice bearing patient-derived ovarian cancer xenografts with different responsiveness to cisplatin. Clin Exp Metastasis. 2015 Oct;32(7):647–658.
  • Investigator’s Brochure for Cediranib, AZD2171, Ed. 17. AstraZeneca Corp. September 11, 2015.
  • Murai J, Huang SY, Das BB, et al. Differential Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588–5599.
  • Azad N, Yu M, Davidson B, et al. Translational predictive biomarker analysis of the phase 1b sorafenib and bevacizumab study expansion cohort. Molecular Cellular Proteomics: MCP. 2013 Jun;12(6):1621–1631.
  • Ning Y-M, Gulley JL, Arlen PM, et al. Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clinical Oncology: Official Journal Am Soc Clin Oncol. 2010 Apr 20;28(12):2070–2076.
  • Park SR, Speranza G, Piekarz R, et al. A multi-histology trial of fostamatinib in patients with advanced colorectal, non-small cell lung, head and neck, thyroid, and renal cell carcinomas, and pheochromocytomas. Cancer Chemother Pharmacol. 2013 Apr;71(4):981–990.
  • Lee JM, Trepel JB, Choyke P, et al. CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer. Front Oncol. 2015;5:123.
  • Reid A, Tang A, Spicer J, et al. An open pharmacokinetic (PK) and mass balance study of 14C-AZD2171, incorporating DCE-CT evaluations. Proc Am Soc Clin Oncol. 2007;25:A14140.
  • Ryan CJ, Stadler WM, Roth B, et al. Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC). Invest New Drugs. 2007 Oct;25(5):445–451.
  • Yamamoto N, Tamura T, Yamamoto N, et al. Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2009 Nov;64(6):1165–1172.
  • Satoh T, Yamaguchi K, Boku N, et al. Phase I results from a two-part Phase I/II study of cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer. Invest New Drugs. 2012 Aug;30(4):1511–1518.
  • Kaye SB, Lubinski J, Matulonis UA, et al. Phase II, Open-Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of Olaparib, a Poly (ADP-Ribose) Polymerase Inhibitor, and Pegylated Liposomal Doxorubicin in Patients With BRCA1 or BRCA2 Mutations and Recurrent Ovarian Cancer. J Clin Oncol. 2012;30(4):372–379.
  • Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382–1392.
  • Ledermann J, Perren T, Raja FE, et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial. Eur J Cancer. 2013;49(Supplement3):LBA10.
  • Moore KN, DiSilvestro P, Lowe ES, et al. SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm). J Clin Oncol. 2014;32(5s):TPS5616.
  • Liu J, Lee J-M, Luo W, et al. A phase 1 study optimizing the dosing of olaparib tablet formulation combined with cediranib in recurrent ovarian cancer. J Clin Oncol. 2015;33:A5559.
  • Chiou VL, Kohn EC, Davarpanah N, et al. Novel Therapeutic Strategies For Angiogenesis Inhibition In Recurrent Ovarian Cancer. Curr Angiogenesis. 2015;3(4):179–192.
  • Plummer R, Swaisland H, Leunen K, et al. Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours. Cancer Chemother Pharmacol. 2015 Oct;76(4):723–729.
  • Travis LB, Holowaty EJ, Bergfeldt K, et al. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N Engl J Med. 1999 Feb 4;340(5):351–357.
  • Bindra RS, Gibson SL, Meng A, et al. Hypoxia-induced down-regulation of BRCA1 expression by E2Fs. Cancer Res. 2005 Dec 15;65(24):11597–11604.
  • Bindra RS, Schaffer PJ, Meng A, et al. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 2004 Oct;24(19):8504–8518.
  • Lu Y, Chu A, Turker MS, et al. Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promoter. Mol Cell Biol. 2011 Aug;31(16):3339–3350.
  • Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur J Cancer. 2007 Sep;43(14):2124–2133.
  • Mehra K, Mehrad M, Ning G, et al. STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis. Front Bioscience. 2011;3:625–634.
  • Menon U, Ryan A, Kalsi J, et al. Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. J Clinical Oncology: Official Journal Am Soc Clin Oncol. 2015 Jun 20;33(18):2062–2071.
  • Patch AM, Christie EL, Etemadmoghadam D, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature. 2015 May 28;521(7553):489–494.
  • Tothill RW, Tinker AV, George J, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research. 2008 Aug 15;14(16):5198–5208.
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182–1186.
  • Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res. 1974 May;34(5):997–1004.
  • Burger RA, Sill MW, Monk BJ, et al. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clinical Oncology: Official Journal Am Soc Clin Oncol 2007 Nov 20;25(33):5165–5171. Erratum in: J Clin Oncol. 2014 Nov 10;32(32):3686.
  • Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clinical Oncology: Official Journal Am Soc Clin Oncol 2007 Nov 20;25(33):5180–5186. Erratum in: J Clin Oncol. 2008 Apr 1;26(10):1773.
  • Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473–2483.
  • Oza AM, Cibula D, Benzaquen AO, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015 Jan;16(1):87–97.
  • Aghajanian C, Blank SV, Goff BA, 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 Clinical Oncology: Official Journal Am Soc Clin Oncol. 2012 Jun 10;30(17):2039–2045.
  • Poveda AM, Selle F, Hilpert F, et al. Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol. 2015;33:3836–3838.
  • McLornan DP, List A, Mufti GJ. Applying synthetic lethality for the selective targeting of cancer. N Engl J Med. 2014 Oct 30;371(18):1725–1735.
  • Economopoulou M, Langer HF, Celeste A, et al. Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med. 2009 May;15(5):553–558.
  • Scanlon SE, Glazer PM. Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment. DNA Repair. 2015 Aug;32:180–189.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.