The efficacy of trabectedin in treating ovarian cancer

Expert Opinion on Pharmacotherapy

Volumn 18, Issue 3, 2017, Pages 313-323

  Teplinsky, Eleonora ^a   Herzog, Thomas J ^b,c  

^a North Shore Long Island Center for Advanced Medicine   (United States)

^b UNIVERSITY OF CINCINNATI   (United States)

^c UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

BRCA; DNA repair pathways; ovarian cancer; pegylated liposomal doxorubicin; platinum resistant; platinum sensitive; recurrent ovarian cancer; Trabectedin

Indexed keywords

BIOLOGICAL MARKER; TRABECTEDIN; 1,3 DIOXOLANE DERIVATIVE; ALKYLATING AGENT; DOXORUBICIN; MACROGOL DERIVATIVE; TETRAHYDROISOQUINOLINE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; FEMALE; HUMAN; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANALOGS AND DERIVATIVES; CHEMICALLY INDUCED; CHEMISTRY; DISEASE FREE SURVIVAL; DRUG DEVELOPMENT; DRUG EFFECTS; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEUTROPENIA; OVARIAN NEOPLASMS; PATHOLOGY; TUMOR MICROENVIRONMENT; TUMOR RECURRENCE;

ANTINEOPLASTIC AGENTS, ALKYLATING; CLINICAL TRIALS, PHASE III AS TOPIC; DIOXOLES; DISEASE-FREE SURVIVAL; DOXORUBICIN; DRUG DISCOVERY; FEMALE; HUMANS; NEOPLASM RECURRENCE, LOCAL; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEUTROPENIA; OVARIAN NEOPLASMS; POLYETHYLENE GLYCOLS; TETRAHYDROISOQUINOLINES; TUMOR MICROENVIRONMENT;

EID: 85011807490     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1080/14656566.2017.1285282     Document Type: Review

References (65)

1. Prevention CfDCa. Ovarian cancer statistics 2015. Available from:https://www.cdc.gov/cancer/ovarian/statistics/.
2. Foley OW, Rauh-Hain JA, del carmen MG., Recurrent epithelial ovarian cancer:an update on treatment. Oncology (Williston Park). 2013;27(4):288-94, 298.
3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.
4. Alvarez RD, Matulonis UA, Herzog TJ, et al. Moving beyond the platinum sensitive/resistant paradigm for patients with recurrent ovarian cancer. Gynecol Oncol. 2016;141(3):405–409.• This paper describes the need for innovation in ovarian cancer, specifically, using identified molecular alterations in recurrent ovarian cancer to aid in the management and treatment of patients.
5. Alvarez RD, Karlan BY, Strauss JF. “Ovarian cancers:evolving paradigms in research and care”:report from the Institute of Medicine. Gynecol Oncol. 2016;141(3):413–415.
6. Cuevas C, Francesch A. Development of Yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep. 2009;26(3):322–337.
7. Larsen AK, Galmarini CM, D’Incalci M. Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol. 2016;77(4):663–671.• This paper provides an excellent review of the mechanism of action of trabectedin.
8. Administration USFaD. FDA news release:FDA approves new therapy for certain types of advanced soft tissue sarcoma. 2015. Available from:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468832.htm.
9. Demetri GD, Von Mehren M, Jones RL, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy:results of a phase III randomized multicenter clinical trial. J Clin Oncol Res. 2016;34(8):786–793.
10. D’Incalci M, Galmarini CM. A review of trabectedin (ET-743):a unique mechanism of action. Mol Cancer Ther. 2010;9(8):2157–2163.
11. Tavecchio M, Simone M, Erba E, et al. Role of homologous recombination in trabectedin-induced DNA damage. Eur J Cancer. 2008;44(4):609–618.
12. Takebayashi Y, Pourquier P, Zimonjic DB, et al. Antiproliferative activity of Ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med. 2001;7(8):961–966.
13. Damia G, Imperatori L, Stefanini M, et al. Sensitivity of CHO mutant cell lines with specific defects in nucleotide excision repair to different anti-cancer agents. Int J Cancer. 1996;66(6):779–783.
14. Zewail-Foote M, Li VS, Kohn H, et al. The inefficiency of incisions of Ecteinascidin 743-DNA adducts by the UvrABC nuclease and the unique structural feature of the DNA adducts can be used to explain the repair-dependent toxicities of this antitumor agent. Chem Biol. 2001;8(11):1033–1049.
15. Colmegna B, Uboldi S, Frapolli R, et al. Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin. Br J Cancer. 2015;113(12):1687–1693.
16. Leporini C, Patane M, Saullo F, et al. A comprehensive safety evaluation of trabectedin and drug-drug interactions of trabectedin-based combinations. BioDrugs. 2014;28(6):499–511.
17. Dossi R, Frapolli R, di Giandomenico S, et al. Antiangiogenic activity of trabectedin in myxoid liposarcoma:involvement of host TIMP-1 and TIMP-2 and tumor thrombospondin-1. Int J Cancer. 2015;136(3):721–729.
18. Germano G, Frapolli R, Simone M, et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Research. 2010;70(6):2235–2244.
19. Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23(2):249–262.
20. Allavena P, Signorelli M, Chieppa M, et al. Anti-inflammatory properties of the novel antitumor agent Yondelis (trabectedin):inhibition of macrophage differentiation and cytokine production. Cancer Research. 2005;65(7):2964–2971.
21. Perez-Ruixo JJ, Zannikos P, Hirankarn S, et al. Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients. Clin Pharmacokinet. 2007;46(10):867–884.
22. Brandon EF, Meijerman I, Klijn JS, et al. In-vitro cytotoxicity of ET-743 (trabectedin, Yondelis), a marine anti-cancer drug, in the Hep G2 cell line:influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction. Anticancer Drugs. 2005;16(9):935–943.
23. Mascilini F, Amadio G, Di Stefano MG, et al. Clinical utility of trabectedin for the treatment of ovarian cancer:current evidence. Onco Targets Ther. 2014;7:1273–1284.
24. JanssenMD. Full prescribing information for YONDELIS® (trabectedin) 2016 [cited 2016 December9]. Available from:https://www.janssenmd.com/pdf/yondelis/YONDELIS_PI.pdf.
25. Beumer JH, Rademaker-Lakhai JM, Rosing H, et al. Metabolism of trabectedin (ET-743, Yondelis) in patients with advanced cancer. Cancer Chemother Pharmacol. 2007;59(6):825–837.
26. Chuk MK, Balis FM, Fox E. Trabectedin. Oncologist. 2009;14(8):794–799.
27. Hing J, Perez-Ruixo JJ, Stuyckens K, et al. Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of trabectedin (ET-743, Yondelis) induced neutropenia. Clin Pharmacol Ther. 2008;83(1):130–143.
28. van Kesteren C, Cvitkovic E, Taamma A, et al. Pharmacokinetics and pharmacodynamics of the novel marine-derived anticancer agent Ecteinascidin 743 in a phase I dose-finding study. Clin Cancer Res. 2000;6(12):4725–4732.•• This phase I study demonstrates the safety and tolerability of the combination of trabectedin and PLD in advanced malignancies.
29. Fetterly GJ, Owen JS, Stuyckens K, et al. Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment. Cancer Chemother Pharmacol. 2008;62(1):135–147.
30. Thertulien R, Manikhas GM, Dirix LY, et al. Effect of trabectedin on the QT interval in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2012;69(2):341–350.
31. Valoti G, Nicoletti MI, Pellegrino A, et al. Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts. Clin Cancer Res. 1998;4(8):1977–1983.
32. Ryan DP, Supko JG, Eder JP, et al. Phase I and pharmacokinetic study of Ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. Clin Cancer Res. 2001;7(2):231–242.
33. Taamma A, Misset JL, Riofrio M, et al. Phase I and pharmacokinetic study of Ecteinascidin-743, a new marine compound, administered as a 24-hour continuous infusion in patients with solid tumors. J Clin Oncol Res. 2001;19(5):1256–1265.
34. Villalona-Calero MA, Eckhardt SG, Weiss G, et al. A phase I and pharmacokinetic study of Ecteinascidin-743 on a daily x 5 schedule in patients with solid malignancies. Clin Cancer Res. 2002;8(1):75–85.
35. van Kesteren C, Twelves C, Bowman A, et al. Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study. Anticancer Drugs. 2002;13(4):381–393.
36. Twelves C, Hoekman K, Bowman A, et al. Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. Eur J Cancer. 2003;39(13):1842–1851.
37. Forouzesh B, Hidalgo M, Chu Q, et al. Phase I and pharmacokinetic study of trabectedin as a 1- or 3-hour infusion weekly in patients with advanced solid malignancies. Clin Cancer Res. 2009;15(10):3591–3599.•• This phase II study concludes that a 3-h infusion schedule of trabectedin in ovarian cancer is less toxic than a 24-h infusion schedule.
38. Pardo B, Salazar R, Ciruelos E, et al. Phase I and pharmacokinetic study of trabectedin 3-hour infusion every three weeks in patients with advanced cancer and alteration of hepatic function. Med Oncol. 2012;29(3):2240–2250.
39. von Mehren M, Schilder RJ, Cheng JD, et al. A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies. Ann Oncol. 2008;19(10):1802–1809.
40. Chu Q, Mita A, Forouzesh B, et al. Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res. 2010;16(9):2656–2665.
41. Vidal L, Magem M, Barlow C, et al. Phase I clinical and pharmacokinetic study of trabectedin and carboplatin in patients with advanced solid tumors. Invest New Drugs. 2012;30(2):616–628.
42. Gore L, Rivera E, Basche M, et al. Phase I combination study of trabectedin and capecitabine in patients with advanced malignancies. Invest New Drugs. 2012;30(5):1942–1949.
43. Sessa C, Cresta S, Noberasco C, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin in solid tumours. Eur J Cancer. 2009;45(12):2116–2122.
44. Sessa C, del Conte G, Christinat A, et al. Phase I clinical and pharmacokinetic study of trabectedin and cisplatin given every three weeks in patients with advanced solid tumors. Invest New Drugs. 2013;31(5):1236–1243.
45. von Mehren M, Bookman M, Meropol NJ, et al. Phase I study of the safety and pharmacokinetics of trabectedin with docetaxel in patients with advanced malignancies. Cancer Chemother Pharmacol. 2015;75(5):1047–1055.
46. Sessa C, de Braud F, Perotti A, et al. Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails. J Clin Oncol Res. 2005;23(9):1867–1874.
47. Krasner CN, McMeekin DS, Chan S, et al. A phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007;97(12):1618–1624.
48. del Campo JM, Roszak A, Bidzinski M, et al. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol. 2009;20(11):1794–1802.
49. del Campo JM, Sessa C, Krasner CN, et al. Trabectedin as single agent in relapsed advanced ovarian cancer:results from a retrospective pooled analysis of three phase II trials. Med Oncol. 2013;30(1):435.•• This pooled analysis describes the outcomes and safety of three phase II trials of single-agent trabectedin in recurrent ovarian cancer.
50. Lorusso D, Scambia G, Pignata S, et al. Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients:the MITO 15 trial. Ann Oncol. 2016;27(3):487–493.
51. Powell SN, Kachnic LA. Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene. 2003;22(37):5784–5791.
52. Monk BJ, Sill MW, Hanjani P, et al. Docetaxel plus trabectedin appears active in recurrent or persistent ovarian and primary peritoneal cancer after up to three prior regimens:a phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 2011;120(3):459–463.• This phase II trial demonstrated that the combination of docetaxel and trabectedin in recurrent ovarian cancer was safe with clinical activity and warrants further study.
53. Monk BJ, Herzog TJ, Kaye SB, et al. Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer. J Clin Oncol Res. 2010;28(19):3107–3114.•• The OVA-301 phase III trial evaluated PLD plus trabectedin versus pegylated PLD alone in relapsed ovarian cancer; the combination arm led to an increase in progression-free survival.
54. Takahashi N, Li WW, Banerjee D, et al. Sequence-dependent enhancement of cytotoxicity produced by Ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells. Clin Cancer Res. 2001;7(10):3251–3257.
55. Meco D, Colombo T, Ubezio P, et al. Effective combination of ET-743 and doxorubicin in sarcoma:preclinical studies. Cancer Chemother Pharmacol. 2003;52(2):131–138.
56. Monk BJ, Herzog TJ, Kaye SB, et al. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer:overall survival analysis. Eur J Cancer. 2012;48(15):2361–2368.•• This paper presents the final survival analysis from the OVA-301 phase III trial.
57. Poveda A, Vergote I, Tjulandin S, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer:outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol. 2011;22(1):39–48.
58. Kaye SB, Colombo N, Monk BJ, et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval. Ann Oncol. 2011;22(1):49–58.
59. Monk BJ, Kaye SB, Poveda A, et al. Nibrin is a marker of clinical outcome in patients with advanced serous ovarian cancer treated in the phase III OVA-301 trial. Gynecol Oncol. 2014;132(1):176–180.
60. Monk BJ, Ghatage P, Parekh T, et al. Effect of BRCA1 and XPG mutations on treatment response to trabectedin and pegylated liposomal doxorubicin in patients with advanced ovarian cancer:exploratory analysis of the phase 3 OVA-301 study. Ann Oncol. 2015;26(5):914–920.• This exploratory analysis of the OVA-301 trial demonstrated that the presence of a BRCA1 mutation may be a marker of predicted efficacy when treated with trabectedin and PLD, especially in patients with platinum-sensitive disease.
61. Pignata SS, Scambia G, Raspagliesi F, et al. The MITO8 phase III international multicenter randomized study testing the effect on survival of prolonging platinum-free interval (PFI) in patients with ovarian cancer (OC) recurring between 6 and 12 months after previous platinum-based chemotherapy:a collaboration of MITO, MANGO, AGO, BGOG, ENGOT, and GCIG. J Clin Oncol Res. 2016; 34(suppl;abstr 5505).• The phase III MITO8 trial demonstrated that prolonging the platinum-free interval with non-platinum-based therapy did not improve outcomes in patients with ovarian cancer who recurred between 6 and 12 months.
62. Sehouli J, Alfaro V, Gonzalez-Martin A. Trabectedin plus pegylated liposomal doxorubicin in the treatment of patients with partially platinum-sensitive ovarian cancer:current evidence and future perspectives. Ann Oncol. 2012;23(3):556–562.
63. Clinicaltrials.gov. Phase III international, randomized study of trabectedin plus pegylated liposomal doxorubicin (PLD) versus carboplatin plus PLD in patients with ovarian cancer progressing within 6-12 months of last platinum (NCT01379989). 2016. Available from:https://clinicaltrials.gov/ct2/show/NCT01379989.• This ongoing phase III trial is evaluating PLD plus carboplatin versus PLD plus trabectedin in ovarian cancer patients progressing within 6–12 months of their last platinum therapy.
64. Clinicaltrials.gov. Multicenter, randomized, non-comparative, open-label phase II trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in adult women with platinum partially sensitive recurring ovarian cancer (NCT01735071). 2016. Available from:https://clinicaltrials.gov/ct2/show/NCT01735071.
65. Clinicaltrials.gov. A study comparing the combination of trabectedin (Yondelis) and Doxil/Caelyx with Doxil/Caelyx for the treatment of advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer (NCT01846611). 2016. [cited 2016 July21]. Available from:https://clinicaltrials.gov/ct2/show/NCT01846611.• This ongoing phase III trial is evaluating PLD plus trabectedin versus PLD alone in ovarian cancer platinum-sensitive patients with two prior lines of platinum-based chemotherapy.