Abstract
Preliminary results of a phase III trial comparing trebananib and paclitaxel with a placebo and paclitaxel in about 900 women with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer show a statistically significant advantage of 1.8 months in median progression-free survival for women enrolled in the trebananib arm versus the control arm.
For years, the antiangiogenesis strategy for treating tumors has been virtually synonymous with anti-VEGF and anti–VEGF receptor (VEGFR) agents such as bevacizumab (Avastin; Genentech) and sunitinib (Sutent; Pfizer). Now, inhibition of the angiogenesis-promoting growth factor angiopoietin may be poised to join anti-VEGF/VEGFR in the cancer armamentarium.
In June, Amgen, of Thousand Oaks, CA, announced encouraging early results from the phase III Trinova-1 trial, which is testing the angiopoietin inhibitor trebananib (AMG 386) in treating recurrent ovarian cancer.
Trinova-1 is comparing trebananib and paclitaxel with a placebo and paclitaxel in about 900 women with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. (Amgen did not disclose the number of women in each group.) Preliminary results show a statistically significant advantage of 1.8 months (7.2 months compared with 5.4 months) in median progression-free survival (PFS) for women enrolled in the trebananib arm compared with the control arm.
“All the different ways of targeting VEGF/VEGFR—ligands and receptors—are far along—in phase III trials or even approved,” comments Laura Benjamin, PhD, vice president of cancer biology and angiogenesis at Imclone Systems in New York, NY, which also studies angiogenesis inhibitors. “The most mature next pathway that is being tackled does appear to be angiopoietin-2.”
The initial result from the Trinova-1 trial “is a real nice finding—that there is an on-treatment benefit for another pathway involved in angiogenesis,” says Benjamin.
Trebananib targets both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), secreted ligands for the Tie2 receptor expressed by vascular endothelial cells. When Ang-1 binds to Tie2, it activates a signaling pathway that contributes to blood vessel stability and integrity. What Ang-2 does is not as well understood, but it also may play a proangiogenic role.
Meanwhile, Amgen has two other phase III trials of trebananib under way, both treating women with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Another Amgen angiopoietin inhibitor, AMG 780, is in a phase I trial. Pfizer, AstraZeneca, and a Regeneron/Sanofi partnership also have angiopoietin inhibitors in early clinical trials.
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