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Trebananib plus paclitaxel extended PFS in recurrent epithelial ovarian cancer
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The addition of trebananib to weekly paclitaxel significantly extended PFS in women with recurrent epithelial ovarian cancer, according to results of a double blind, placebo-controlled phase 3 trial.
Researchers observed increased incidence of edema with trebananib (AMG 386, Amgen) compared with placebo, but differences in other adverse events typically associated with anti-vascular endothelial growth factor agents were minimal between the two study arms.
Bradley J. Monk
“The results from the TRINOVA-1 study are clinically significant because they validate both a new target and a new therapeutic agent in the setting of epithelial ovarian cancer,” Bradley J. Monk, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, and colleagues wrote. “Trebananib plus paclitaxel might provide a non-vascular endothelial growth factor anti-angiogenesis treatment option to women with recurrent epithelial ovarian cancer, if approved by regulatory agencies.”
The analysis included 919 women with recurrent epithelial ovarian cancer. All patients had undergone three or fewer prior treatments and had a platinum-free interval of less than 12 months.
Monk and colleagues randomly assigned 461 women to weekly 80 mg/m2 paclitaxel plus weekly 15 mg/kg trebananib. The other 458 women received paclitaxel plus placebo.
PFS in the intention-to-treat population served as the primary outcome measure.
During median follow-up of 10.1 months, 52% of patients assigned trebananib and 71% of patients assigned placebo experienced disease progression.
Researchers reported significantly longer median PFS in the trebananib arm (7.2 months vs. 5.4 months; HR=.66; 95% CI, 0.57-0.77).
Results of an interim analysis showed a trend toward longer OS in the trebananib arm (19 months vs. 17.3 months; HR=0.86; 95% CI, 0.69-1.08), but the difference was not statistically significant.
Incidence of grade ≥3 adverse events were similar between the two arms (56% for trebananib vs. 54% for placebo); however, more patients assigned trebananib discontinued treatment due to adverse events (17% vs. 6%).
Researchers reported higher incidence of any-grade edema (64% vs. 28%) in the trebananib arm. The difference in other adverse events typically associated with anti-VEGF therapy — such as hypertension, proteinuria, thrombotic events, gastrointestinal perforations and wound-healing complications — was less than 2% between study arms.
Bleeding incidence was higher in the placebo arm (17% vs. 10%).
In an accompanying editorial, Charlie Gourley, MD, PhD, of the University of Edinburgh Cancer Research UK Center and the MRC Institute of Genetics and Molecular Medicine at Western General Hospital in Edinburgh, commended the researchers for restricting their study to patients with high-grade serous and endometrioid ovarian cancer.
“Most ovarian cancer studies of anti-angiogenic agents have included all epithelial cancer subtypes, despite their clear biological differences,” Gourley wrote. “Recent data from two studies have suggested that patients with ovarian cancer can be stratified on a molecular basis according to their level of benefit from bevacizumab [Avastin, Genentech],” he said. “If those findings hold true and are also applicable to other anti-angiogenic drugs, then this might allow anti-angiogenic treatment to be restricted to the patients most likely to benefit, and studies investigating combinations and treatment beyond progression can proceed in earnest.”
For more information:
- Gourley C. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70283-9.
- Monk BJ. Lancet Oncol. 2014;doi:10.1016/S1470-2045(14)70244-X.
Disclosure: The study was funded by Amgen. The researchers report research funding from Amgen and Sanofi; employment relationships with, steering committee roles with and stock ownership in Amgen; advisory board roles with AstraZeneca, Chugai-Roche, GlaxoSmithKline, Merck and Zeria Pharma; and honoraria from Chugai-Roche, Kyowa-Kirin, Morphotek and Taiho. Gourley reports grants or personal fees from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Pharma Mar and Roche.