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AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney
Author(s) -
Rini Brian,
Szczylik Cezary,
Tannir Nizar M.,
Koralewski Piotr,
Tomczak Piotr,
Deptala Andrzej,
Dirix Luc Y.,
Fishman Mayer,
Ramlau Rodryg,
Ravaud Alain,
Rogowski Wojciech,
Kracht Karolyn,
Sun YuNien,
Bass Michael B.,
Puhlmann Markus,
Escudier Bernard
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27632
Subject(s) - medicine , sorafenib , renal cell carcinoma , clinical endpoint , tolerability , adverse effect , gastroenterology , hazard ratio , placebo , progression free survival , urology , randomized controlled trial , oncology , surgery , confidence interval , hepatocellular carcinoma , chemotherapy , pathology , alternative medicine
Abstract BACKGROUND: This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin‐1 and angiopoietin‐2 with Tie2 (tyrosine kinase with immunoglobulin‐like and EGF‐like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study. METHODS: Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open‐label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression‐free survival (PFS). RESULTS: A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60‐1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%‐53%), 37% (24%‐52%), and 25% (14%‐40%). Among 30 patients in arm C who had disease progression and subsequently received open‐label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%‐17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar‐plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386. CONCLUSIONS: In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib. Cancer 2012. © 2012 American Cancer Society.