In a phase II study reported in the Journal of Clinical Oncology, Atkins et al found that combined treatment with the recombinant peptide-Fc fusion protein trebananib and the vascular endothelial growth factor (VEGF) inhibitor sunitinib (Sutent) was active in metastatic renal cell cancer and appeared to increase toxicity compared with the established side effect profile of sunitinib. Trebananib exerts an antiangiogenic effect by binding to angiopoietin-1 and angiopoietin-2, a mechanism that differs from that of sunitinib.
In the study, patients were sequentially enrolled in cohorts receiving sunitinib 50 mg once daily for 4 weeks on and 2 weeks off and intravenous trebananib once weekly at 10 mg/kg (n = 43) or 15 mg/kg (n = 42). The primary endpoints were incidence of adverse events and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary endpoints included objective response rate and progression-free survival.
During the first 12 weeks of treatment, 58% of patients in the trebananib 10 mg/kg group and 57% of those in the 15 mg/kg group had sunitinib dose interruptions. The most common treatment-related adverse events of any grade were diarrhea (74% and 67%), mucosal inflammation (49% and 60%), and hypertension (52% and 45%). Adverse events ≥ grade 3 occurred in 58% and 69%, including hypertension in 32% and 24%, palmar-plantar erythrodysesthesia syndrome in 19% and 2%, fatigue in 7% and 17%, and asthenia in 5% and 14%.
The objective response rate was 58% in the 10-mg/kg group and 63% in the 15-mg/kg group (all partial responses), and median progression-free survival was 13.9 months (95% confidence interval [CI] = 10.4–19.2 months) and 16.3 months (95% CI = 13.1–21.4 months). Median overall survival was 36 months (95% CI = 25.2 months to not estimable) in the 10-mg/kg group and not estimable with a median follow-up of 25 months in the 15-mg/kg group.
The investigators concluded: “Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.”
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by Amgen. For full disclosures of the study authors, visit jco.ascopubs.org.
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