A safety study of trebananib (AMG 386) and abiraterone in metastatic castration-resistant prostate cancer.

Abstract

218 Background: Trebananib is an angiopoietin1/2 antagonist peptibody. Androgens stimulate expression of VEGF via activation of hypoxia inducible factor-a (HIFa). Androgen deprivation therapy (ADT) is associated with lower HIF1a gene expression in prostate cancer tissue. Dual targeting of the androgen and angiogenic axis represents a potential synergistic anti-angiogenic therapeutic approach in metastatic castration resistant prostate cancer (mCRPC). In this preliminary safety study we hypothesize that trebananib in combination with abiraterone will have a favorable tolerability and efficacy profile. Methods: Patients with mCRPC were treated with abiraterone 1000mg daily and prednisone 5 mg twice daily. Trebananib was administered intravenously every week, in escalating doses from 15mg/kg to 30mg/kg on days 1, 8, 15, and 22 every 28-days. Results: A total of 9 patients were enrolled. Three of nine patients had prior chemotherapy. The median age was 63.8 (63-71yrs). No dose limiting toxicities were observed. The most common grade ≥ 2 toxicities included limb edema (3/9), hyperglycemia (1/9), gastrointestinal (2/9), fatigue (2/9), hypertension (1/9), confusion (1/9), weight gain (1/9) and insomnia (2/9). 5/9 of patients had an overall PSA decline of >30%. 8/9 patients were evaluable for response. Prior chemotherapy patients were on study for 1 and 3 months. No prior chemotherapy patients were treated for 1, 6, 9, 10, 10, and 17 months. Conclusions: Trebananib in combination with abiraterone is well tolerated and displayed an acceptable safety profile in patients with mCRPC. Based on this safety data a randomized phase II study randomizing chemotherapy-naïve mCRPC patients to either abiraterone/prednisone plus AMG 386 at 30mg/kg or abiraterone/prednisone is currently accruing at the NCI. Clinical trial information: NCIT01553188.

New advances in genitourinary cancer: evidence gathered in 2014

“…In a safety study of trebananib and abiraterone in metastatic castration-resistant prostate cancer, this combination has shown a good toxicity profile [24]. A randomized phase 2 study is ongoing.…”

“…Local therapy was administered at 3 months, and 413 patients were accrued. With a median follow-up of 7.6 years, progression-free survival (PFS) was marginally improved in the ADT+DE arm: 8-year PFS rate=62 % [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] in the ADT+DE arm vs. 53 % [8][9][10][11][12][13][23][24][25][26][27][28][29][30][31][32] in the ADT arm. Docetaxel-estramustine is associated with a borderline significant reduction in the risk of relapse or death in high-risk prostate cancer.…”