CHICAGO—The phase 3 RILOMET-1 study of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy for patients with advanced MET-positive gastric or gastroesophageal junction (GEJ) cancer did not meet its primary end point, overall survival (OS), results presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting have shown.1
This lack of efficacy was due to an increase of deaths in the rilotumumab arm due to disease progression and was regardless of the level of MET-positive expression, said David Cunningham, MD, of the Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
Previously, a phase 2 study2 had shown improved overall survival (OS) and progression-free survival (PFS) with rilotumumab, a fully human monoclonal antibody to hepatocyte growth factor, plus ECX compared with placebo in this population.
In the RILOMET-1 trial, patients with pathologically confirmed unresectable advanced gastric or GEJ adenocarcinoma were randomly assigned 1:1 to ECX (IV epirubicin 50 mg/m2 day 1, IV cisplatin 60 mg/m2 day 1, oral capecitabine 625 mg/m2 twice daily, days 1−21) plus rilotumumab 15 mg/kg or placebo IV every 3 weeks. All patients had tumors positive for MET and were and stratified by disease extent (locally advanced vs. metastatic) and ECOG score (0 vs. 1).
Secondary end points included progression-free survival (PFS), 12-month survival rate, overall response rate (ORR), safety, and pharmacokinetics.
From November 2012 to November 2014, 609 patients were randomly assigned into the trial, 304 patients received rilotumumab plus ECX and 305 patients received placebo plus ECX. The study was stopped early based on an imbalance in deaths in the fourth preplanned review of safety data (93 deaths in the rilotumumab arm vs. 75 deaths in the placebo arm at a data cutoff date of November 3, 2014).
Results showed that rilotumumab was not superior to placebo for OS; in addition, PFS and ORR were statistically worse in the rilotumumab arm.
Median OS was 9.6 months (range: 7.9-11.4 months) in the rilotumumab arm and 11.5 months (range: 9.7-13.1 months) in the placebo arm (unstratified HR: 1.36 [1.05,1.75]; P=0.021). Median PFS was 5.7 months (range: 5.3-5.9 months) in the rilotumumab arm and 5.7 months (range: 5.5-7.1 months) in the placebo arm (unstratified HR: 1.27 [1.03,1.58]; P=0.025).
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The ORR was 30.0% in the rilotumumab arm and 39.2% in the placebo arm (P=0.03) and the disease control rate was 54.0% compared with 64.9%, respectively, (P=0.01).
The most common adverse events that were higher with rilotumumab were peripheral edema, hypoalbuminemia, deep vein thrombosis, and hypocalcemia.
”Further analysis is warranted to understand the results from a biological and clinical perspective,” Dr. Cunningham said, adding that plasma total HGF analyses are ongoing.
- Cunningham D, Tebbutt NC, Davidenko I, et al. Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study. J Clin Oncol. 2015;33:(suppl; abstr 4000).
- Iveson T, Donehower RC, Davidenko I, et al. Rilotumumab in combination with epirubidin, cisplatin, and capecitabine as first-line treatment for gastroc or oesophagogastric junction adenocarcinoma: an open-label, dose-de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014;15:1007-1018.