ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer

European Journal of Cancer

Volumn 70, Issue , 2017, Pages 111-121

  Marth, Christian ^a   Vergote, Ignace ^b   Scambia, Giovanni ^c   Oberaigner, Willi ^d   Clamp, Andrew ^e   Berger, Regina ^a   Kurzeder, Christian ^f   Colombo, Nicoletta ^g   Vuylsteke, Peter ^h   Lorusso, Domenica ⁱ   Hall, Marcia ^j   Renard, Vincent ^k   Pignata, Sandro ^l   Kristeleit, Rebecca ^m   Altintas, Sevilay ⁿ   Rustin, Gordon ^j   Wenham, Robert M ^o   Mirza, Mansoor Raza ^p   Fong, Peter C ^q   Oza, Amit ^r   Monk, Bradley J ^s   Ma, Haijun ^t   Vogl, Florian D ^t   Bach, Bruce A ^t   more..

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^c FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^d AGO Austria and Department of Clinical Epidemiology of the Tirol Kliniken Ltd   (Austria)

^e UNIVERSITY OF MANCHESTER   (United Kingdom)

^f KLINIKEN ESSEN MITTE   (Germany)

^g EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^h UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

ⁱ NATIONAL CANCER INSTITUTE   (Italy)

^j MOUNT VERNON CANCER CENTRE   (United Kingdom)

^k BGOG and Department of Oncology   (Belgium)

^l NATIONAL CANCER INSTITUTE   (Italy)

^m UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁿ ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^o H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^p University of Copenhagen   (Denmark)

^q AUCKLAND CITY HOSPITAL   (New Zealand)

^r UNIVERSITY OF TORONTO   (Canada)

^s UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^t AMGEN INC   (United States)

more..

Author keywords

Duration of response; ENGOT ov 6 TRINOVA 2; Objective response rate; Pegylated liposomal doxorubicin; Progression free survival; Trebananib

Indexed keywords

DOXORUBICIN; TREBANANIB; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; HYBRID PROTEIN; MACROGOL DERIVATIVE; PLATINUM;

ABDOMINAL PAIN; ADULT; AGED; ARTICLE; ASCITES; BRAIN ISCHEMIA; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURVIVAL; CONTROLLED STUDY; COUGHING; DIGESTIVE SYSTEM PERFORATION; DOUBLE BLIND PROCEDURE; DRUG WITHDRAWAL; EDEMA; FATIGUE; FEMALE; FOLLOW UP; HEART RIGHT VENTRICLE FAILURE; HUMAN; HYPERTENSION; HYPOKALEMIA; INCIDENCE; INFLAMMATION; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; OVARY CARCINOMA; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY FAILURE; THROMBOEMBOLISM; TREATMENT DURATION; TREATMENT RESPONSE; VOMITING; WOUND HEALING IMPAIRMENT; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; DISEASE FREE SURVIVAL; MIDDLE AGED; OVARIAN NEOPLASMS;

ADULT; AGED; ANGIOGENESIS INHIBITORS; ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; DOXORUBICIN; FEMALE; HUMANS; MIDDLE AGED; OVARIAN NEOPLASMS; PLATINUM; POLYETHYLENE GLYCOLS; RECOMBINANT FUSION PROTEINS;

EID: 85002322923     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2016.09.004     Document Type: Article

References (39)

1. [1] NCCN clinical practice guidelines in oncology: ovarian cancer v.2.2015, 2015, National Comprehensive Cancer Network, Fort Washington, PA.
2. [2] Coleman, R.L., Monk, B.J., Sood, A.K., Herzog, T.J., Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol 10 (2013), 211–224, 10.1038/nrclinonc.2013.5.
3. [3] Ozols, R.F., Challenges for chemotherapy in ovarian cancer. Ann Oncol 17:Suppl. 5 (2006), v181–v187, 10.1093/annonc/mdj978.
4. [4] Rose, P.G., Maxson, J.H., Fusco, N., Mossbruger, K., Rodriguez, M., Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages. Gynecol Oncol 82 (2001), 323–328, 10.1006/gyno.2001.6272.
5. [5] Campos, S.M., Penson, R.T., Mays, A.R., Berkowitz, R.S., Fuller, A.F., Goodman, A., et al. The clinical utility of liposomal doxorubicin in recurrent ovarian cancer. Gynecol Oncol 81 (2001), 206–212, 10.1006/gyno.2000.5980.
6. 2) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 78 (2000), 369–372, 10.1006/gyno.2000.5921.
7. [7] Muggia, F.M., Hainsworth, J.D., Jeffers, S., Miller, P., Groshen, S., Tan, M., et al. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 15 (1997), 987–993.
8. [8] Gordon, A.N., Tonda, M., Sun, S., Rackoff, W., Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 95 (2004), 1–8, 10.1016/j.ygyno.2004.07.011.
9. [9] Folkman, J., Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29 (2002), 15–18, 10.1016/S0093-7754(02)70065-1.
10. [10] Augustin, H.G., Koh, G.Y., Thurston, G., Alitalo, K., Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10 (2009), 165–177, 10.1038/nrm2639.
11. [11] Gavalas, N.G., Liontos, M., Trachana, S.P., Bagratuni, T., Arapinis, C., Liacos, C., et al. Angiogenesis-related pathways in the pathogenesis of ovarian cancer. Int J Mol Sci 14 (2013), 15885–15909, 10.3390/ijms140815885.
12. [12] Pujade-Lauraine, E., Hilpert, F., Weber, B., Reuss, A., Poveda, A., Kristensen, G., et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 32 (2014), 1302–1308, 10.1200/JCO.2013.51.4489.
13. [13] Aghajanian, C., Blank, S.V., Goff, B.A., Judson, P.L., Teneriello, M.G., Husain, A., 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 30 (2012), 2039–2045, 10.1200/JCO.2012.42.0505.
14. [14] Coleman, R.L., Brady, M.F., Herzog, T.J., Sabbatini, P., Armstrong, D.K., Walker, J.L., et al. A phase III randomized controlled clinical trial of carboplatin and paclitaxel alone or in combination with bevacizumab followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and fallopian tube cancer (Gynecologic Oncology Group 0213) [abstract]. Gynecol Oncol 137 (2015), 3–4, 10.1016/j.ygyno.2015.01.005.
15. [15] Burger, R.A., Brady, M.F., Bookman, M.A., Fleming, G.F., Monk, B.J., Huang, H., et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365 (2011), 2473–2483, 10.1056/NEJMoa1104390.
16. [16] Perren, T.J., Swart, A.M., Pfisterer, J., Ledermann, J.A., Pujade-Lauraine, E., Kristensen, G., et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365 (2011), 2484–2496, 10.1056/NEJMoa1103799.
17. [17] du Bois, A., Kristensen, G., Ray-Coquard, I., Reuss, A., Pignata, S., Colombo, N., et al. AGO-OVAR 12: a randomized placebo-controlled GCIG/ENGOT-intergroup phase III trial of standard frontline chemotherapy ± nintedanib for advanced ovarian cancer [abstract]. Int J Gyn Cancer, 23, 2013, PL01.
18. [18] du Bois, A., Floquet, A., Kim, J.W., Rau, J., del Campo, J.M., Friedlander, M., et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol 32 (2014), 3374–3382, 10.1200/JCO.2014.55.7348.
19. [19] Ledermann, J.A., Embleton, A.C., Raja, F., Perren, T.J., Jayson, G.C., Rustin, G.J., et al. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 387 (2016), 1066–1074, 10.1016/S0140-6736(15)01167-8.
20. [20] Aghajanian, C., Goff, B., Nycum, L.R., Wang, Y.V., Husain, A., Blank, S.V., 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 139 (2015), 10–16, 10.1016/j.ygyno.2015.08.004.
21. [21] Oliner, J., Min, H., Leal, J., Yu, D., Rao, S., You, E., et al. Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 6 (2004), 507–516, 10.1016/j.ccr.2004.09.030.
22. [22] Coxon, A., Bready, J., Min, H., Kaufman, S., Leal, J., Yu, D., et al. Context-dependent role of angiopoietin-1 inhibition in the suppression of angiogenesis and tumor growth: implications for AMG 386, an angiopoietin-1/2-neutralizing peptibody. Mol Cancer Ther 9 (2010), 2641–2651, 10.1158/1535-7163.MCT-10-0213.
23. [23] Vergote, I., Schilder, R.J., Pippitt, C.H. Jr., Wong, S., Gordon, A.N., Scudder, S., et al. A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Gynecol Oncol 135 (2014), 25–33, 10.1016/j.ygyno.2014.07.003.
24. [24] Karlan, B.Y., Oza, A.M., Richardson, G.E., Provencher, D.M., Hansen, V.L., Buck, M., et al. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol 30 (2012), 362–371, 10.1200/JCO.2010.34.3178.
25. [25] Monk, B.J., Poveda, A., Vergote, I., Raspagliesi, F., Fujiwara, K., Bae, D.S., et al. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15 (2014), 799–808, 10.1016/S1470-2045(14)70244-X.
26. [26] Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R., et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45 (2009), 228–247, 10.1016/j.ejca.2008.10.026.
27. [27] Vergote, I., Pujade-Lauraine, E., Pignata, S., Kristensen, G.B., Ledermann, J., Casado, A., et al. European Network of Gynaecological Oncological Trial Groups' requirements for trials between academic groups and pharmaceutical companies. Int J Gynecol Cancer 20 (2010), 476–478, 10.1111/IGC.0b013e3181d3caa8.
28. [28] Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v3.0 (CTCAE). Available at: http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf. [Accessed 2 December 2015].
29. [29] Cella, D.F., Tulsky, D.S., Gray, G., Sarafian, B., Linn, E., Bonomi, A., et al. The functional assessment of cancer therapy scale: development and validation of the general measure. J Clin Oncol 11 (1993), 570–579.
30. [30] Brooks, R., EuroQol: the current state of play. Health Policy 37 (1996), 53–72.
31. [31] Lin, D.Y., Wei, L.J., Ying, Z., Checking the Cox model with cumulative sums of martingale-based residuals. Biometrika 80 (1993), 557–572, 10.1093/biomet/80.3.557.
32. [32] Eskens, F.A., Verweij, J., The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer 42 (2006), 3127–3139.
33. [33] Pignata, S., Lorusso, D., Scambia, G., Sambataro, D., Tamberi, S., Cinieri, S., et al. MITO-11: a randomized multicenter phase II trial testing the addition of pazopanib to weekly paclitaxel in platinum-resistant or -refractory advanced ovarian cancer (AOC). J Clin Oncol, 32, 2014, 5503.
34. [34] Poveda, A.M., Selle, F., Hilpert, F., Reuss, A., Savarese, A., Vergote, I., 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 33 (2015), 3836–3838, 10.1200/JCO.2015.63.1408.
35. [35] Monk, B.J., Poveda, A., Vergote, I., Raspagliesi, F., Fujiwara, K., Bae, D.S., et al. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol 143 (2016), 27–34.
36. [36] Ferriss, J.S., Java, J.J., Bookman, M.A., Monk, B.J., Walker, J.L., Homesley, H.D., et al. Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG Oncology/GOG study. Gynecol Oncol 139 (2015), 17–22, 10.1016/j.ygyno.2015.07.103.
37. [37] Oza, A.M., Cook, A.D., Pfisterer, J., Embleton, A., Ledermann, J.A., Pujade-Lauraine, E., et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol 16 (2015), 928–936, 10.1016/s1470-2045(15)00086-8.
38. [38] Sangisetty, S.L., Miner, T.J., Malignant ascites: a review of prognostic factors, pathophysiology and therapeutic measures. World J Gastrointest Surg 4 (2012), 87–95.
39. [39] Smolle, E., Taucher, V., Haybaeck, J., Malignant ascites in ovarian cancer and the role of targeted therapeutics. Anticancer Res 34 (2014), 1553–1561.