In renal cell carcinoma (RCC), angiopoietin (Ang) 2 is elevated at the time of progression on anti-vascular endothelial growth factor (VEGF) therapy and may contribute to resistance.
We tested trebananib, an Ang 1 and 2 neutralizing peptibody in patients with RCC progressing on anti-VEGF treatment.
Patients with measurable RCC progressing despite an anti-VEGF agent within 12 weeks, any number of prior treatments, and good PS were randomized to trebananib 15 mg/kg IV weekly without (Arm A) or with (Arm B) continuation of the prior anti-VEGF agent. The primary endpoint for each arm was tumor response (RECIST 1.1). Secondary endpoints included progression free survival and adverse events.
Of 41 enrolled patients, 35 were eligible and started treatment (17 Arm A, 18 Arm B) with median age 60 (46-76) and 3 prior treatments (1-8). Four died prior to documented progression and 27 progressed as their first event. Both arms were stopped after interim analysis, 2 responses (11%; 95% C.I. 1-35%) were observed in Arm B. Median PFS of 2.7 (95% C.I. 2.3-4.7) months in Arm A and 5.2 (95% C.I. 2.7-10.8) months in Arm B did not support continued study. Common adverse events including fatigue, nausea, and increased creatinine were generally grade 1-2 and numerically higher in Arm B. The most common grade 3 or higher adverse events were hypertension and dyspnea.
While tolerable, trebananib either without or with continued anti-VEGF therapy did not show promising activity in RCC patients who recently progressed on anti-VEGF therapy alone.
Kidney cancer. 2019 Feb 05*** epublish ***
Thomas J Semrad, Susan Groshen, Chunqiao Luo, Sumanta Pal, Ulka Vaishampayan, Monika Joshi, David I Quinn, Philip C Mack, David R Gandara, Primo N Lara
Gene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, CA, USA., University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Karmanos Cancer Institute, Detroit, MI, USA., Penn State Milton S. Hershey Medical Center, Hershey, PA, USA., University of California, Davis Comprehensive Cancer Center, Sacramento, CA, USA.