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DI-033 Clinical response of rilotumumab in solid tumours

Background The biology and treatment of cancer have been revolutionised in recent years due to identification of treatable genetic alterations. Alterations in the MET pathway have been associated with poor clinical outcomes in patients with glioblastoma, and colorectal, renal, gastric or prostate cancer. Several MET inhibitors have been developed to block the HGF/MET signalling pathway, such as rilotumumab, a monoclonal antibody that neutralises HGF, blocking MET activation. Purpose To evaluate progression free survival (PFS) and response rate (RR) of rilotumumab in patients with glioblastoma, and colorectal, renal, gastric or prostate cancer in recently published clinical trials. Material and methods Literature review of studies published in 2010–2015, focused on PFS or RR and rilotumumab in glioblastoma and colorectal, renal, gastric or prostate cancer. Results Five clinical trials were included. A phase II trial of 142 patients evaluated rilotumumab in combination with panitumumab, in colon cancer patients with the wild type for KRAS (NCT00788957). The study demonstrated that addition of rilotumumab did not significantly improve outcome, with an RR of 31% for rilotumumab+panitumumab versus 21% for panitumumab as a single agent; PFS was 5.2 vs. 3.7 months, respectively. The combination of rilotumumab with epirubicin, cisplatin and capecitabine (ECX) in a randomised phase II trial of 121 patients with metastatic gastric or oesophagogastric junction (OGJ) cancer did not demonstrated an improvement in PFS (5.6 vs 4.2 months; hazard ratio (HR)=0.61;p = 0.05) or OS (11.1 vs 8.9 months; HR=0.73; p = 0.22) (NCT00719550). However, among patients with high MET levels (>50% of cells with ≥1+ MET staining), the combination of rilotumumab and ECX resulted in a significantly better OS (median 11.1 vs 5.7 months; HR=0.29; p = 0.01) compared with placebo plus ECX. A phase III trial in patients with unresectable metastatic MET positive gastric or OGJ cancer is currently ongoing (NCT01697072). Rilotumumab has been tested in renal cell carcinoma, glioblastoma and prostate cancer but phase II studies have failed to demonstrate significant antitumour activity (NCT00427440, NCT00770848, NCT00422019). Conclusion MET/HGF signalling represents an important target in cancer. Inhibition of this pathway by rilotumumab has showed a clinical response in OGJ patients with MET overexpression. However, in glioblastoma, and colorectal, renal and prostate cancer, rilotumumab has not demonstrated clinical improvement. Thus further studies are required to evaluate rilotumumab efficacy in cancer. No conflict of interest.