Trebananib: an alternative anti-angiogenic strategy

Phase 3 clinical trials have shown a significant benefit for anti-angiogenic treatment in ovarian cancer either in the first line 1 Burger RA Brady MF Bookman MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011; 365: 2473-2483 Crossref PubMed Scopus (1637) Google Scholar , 2 Perren TJ Swart AM Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484-2496 Crossref PubMed Scopus (1513) Google Scholar , 3 Du Bois A Kristensen G Ray-Coquard I et al. A randomized placebo-controlled GCIG/ENGOT-intergroup phase III trial of standard frontline chemotherapy +/- nintedanib for advanced ovarian cancer. Int J Gyn Cancer. 2013; 23 (LBA1 (abstr).) Google Scholar , 4 Du Bois A Floquet A Kim JW et al. Randomised, double-blind phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube or promary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). Proc Am Soc Clin Oncol. 2013; 31 (LBA5503 (abstr).) Google Scholar or relapsed disease settings. 5 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 Clin Oncol. 2012; 30: 2039-2045 Crossref PubMed Scopus (983) Google Scholar , 6 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: 1302-1308 Crossref PubMed Scopus (16) Google Scholar , 7 Ledermann JA Perren TJ Raja FA 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 (LBA 10 (abstr).) Google Scholar Results of the first-line studies have generally shown a modest progression-free survival benefit, with the exception of AGO-OVAR16 4 Du Bois A Floquet A Kim JW et al. Randomised, double-blind phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube or promary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). Proc Am Soc Clin Oncol. 2013; 31 (LBA5503 (abstr).) Google Scholar in which a 5·6-month improvement was more impressive, but came at the expense of marked toxic effects. 4 Du Bois A Floquet A Kim JW et al. Randomised, double-blind phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube or promary peritoneal cancer (AEOC): Results of an international Intergroup trial (AGO-OVAR16). Proc Am Soc Clin Oncol. 2013; 31 (LBA5503 (abstr).) Google Scholar So far, the only study to show a significant overall survival benefit was the ICON6 study, 7 Ledermann JA Perren TJ Raja FA 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 (LBA 10 (abstr).) Google Scholar in which patients with platinum-sensitive, relapsed ovarian cancer were given concomitant and maintenance cediranib. The proportion of patients given anti-angiogenic agents who achieved a tumour response was consistently between 15–21% in these studies, 2 Perren TJ Swart AM Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484-2496 Crossref PubMed Scopus (1513) Google Scholar , 5 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 Clin Oncol. 2012; 30: 2039-2045 Crossref PubMed Scopus (983) Google Scholar , 6 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: 1302-1308 Crossref PubMed Scopus (16) Google Scholar and these findings, in addition to the well-documented single-agent activity, further emphasise the validity of this approach. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trialInhibition of angiopoietins 1 and 2 with trebananib provided a clinically meaningful prolongation in progression-free survival. This non-VEGF anti-angiogenesis option for women with recurrent epithelial ovarian cancer should be investigated in other settings and in combination with additional agents. Although oedema was increased, typical anti-VEGF associated adverse events were not prominent. Full-Text PDF