Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress.
—Timothy Iveson, MD, and colleagues
Hepatocyte growth factor (HGF) and its receptor MET have been found to promote the proliferation, migration, and survival of tumor cells and to play a role in gastric cancer. In a phase II study reported in The Lancet Oncology, Timothy Iveson, MD, of the University Hospital Southampton NHS Foundation Trust, United Kingdom, and colleagues found evidence of benefit from adding the investigational anti-HGF monoclonal antibody rilotumumab to epirubicin, cisplatin, and capecitabine (ECX) in first-line treatment of advanced gastric or esophagogastric junction cancer.1
In this double-blind study, 121 patients with unresectable disease were randomly assigned to receive rilotumumab at 15 mg/kg (n = 40) or 7.5 mg/ kg (n = 42) or placebo (n = 39) on day 1 in combination with ECX (epirubicin at 50 mg/m2 on day 1, cisplatin at 60 mg/m2 on day 1, capecitabine at 625 mg/m2 twice a day on days 1–21) every 3 weeks. The primary endpoint was progression-free survival.
The three treatment groups were genrally balanced for age (median, 59–62 years), sex (68%–79% male), race/ethnicity (69%–83% white), Eastern Cooperative Oncology Group performance status (0 in 36%–48%, 1 in 53%–62%), primary tumor location (gastric in 79%–83%), disease extent (metastatic in 87%–90%), previous curative surgery (15%–23%), previous radiotherapy (2%–8%), and previous adjuvant (3%–5%) and neoadjuvant chemotherapy (5% in all).
Increased Progression-Free Survival
Median follow-up was 21.7 months. Median progression-free survival was 5.1 months in the rilotumumab at 15 mg/kg group (hazard ratio [HR] = 0.69, P = .164, vs placebo), 6.8 months in the 7.5 mg/kg group (HR = 0.53, P = .009), and 5.7 months in the combined groups (HR = 0.60, P = .016) vs 4.2 months in the placebo group.
Objective response occurred in 31%, 48%, 39%, and 21% of patients, in the 15 mg/kg of rilotumumab, 7.5 mg/kg, combined, and placebo groups, respectively. Median overall survival was 9.7 months (HR = 0.68, P = .149), 11.1 months (HR = 0.79, P = .354), 10.6 months (HR = 0.70, P = .109), and 8.9 months, respectively.
Adverse events of any grade that were more common in the rilotumumab combination group than in the placebo group included hematologic adverse events (neutropenia in 54% vs 33%, anemia in 40% vs 28%, and thrombocytopenia in 11% vs 0%), peripheral edema (27% vs 8%), and venous thromboembolism (20% vs 13%). Grade 3 or 4 adverse events that were more common in rilotumumab patients included neutropenia (44% vs 28%) and venous thromboembolism (20% vs 10%).
Serious adverse events were similar in the treatment groups except for a greater frequency of anemia (12% vs 0%) with rilotumumab. Adverse events led to dose reduction or interruption in 14% of the combined rilotumumab group vs 8% of the placebo group and discontinuation of treatment in 27% vs 8%.
The investigators concluded, “Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress.” ■
Disclosure: The study was funded by Amgen Inc. For full disclosures of the study authors, visit www.thelancet.com.
1. Iveson T, Donehower RC, Davidenko I, et al: Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: An open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. June 23, 2014 (early release online).