Eli Lilly has announced that the RAISE trial, a phase III study of ramucirumab (CYRAMZA) in combination with chemotherapy in patients with metastatic colorectal cancer (mCRC), met its primary endpoint of overall survival. The global, randomized, double-blind study compared ramucirumab plus FOLFIRI to placebo plus FOLFIRI as a second-line treatment in patients with mCRC after treatment with bevacizumab, oxaliplatin and a fluoropyrimidine in the first-line setting.

RAISE showed a statistically significant improvement in overall survival in patients treated with ramucirumab plus FOLFIRI compared to placebo plus FOLFIRI. The study also showed a statistically significant improvement in progression-free survival in the ramucirumab-plus-FOLFIRI arm compared to the placebo-plus-FOLFIRI arm. The most common (>5% incidence) grade >/=3 adverse events occurring at a higher rate on the ramucirumab-plus-FOLFIRI arm compared to the control arm were neutropenia, fatigue, hypertension, and diarrhea.

Despite advances in treating colorectal cancer in recent years, the mortality rate remains significant. It is the fourth leading cause of cancer death worldwide and the second leading cause of cancer death in the U.S.

"Patients with metastatic colorectal cancer—particularly those in the second-line setting—continue to need new treatment options that improve survival," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "We are pleased that the RAISE study demonstrated a survival benefit and are hopeful that ramucirumab will become a new anti-angiogenic treatment option after first-line bevacizumab-containing therapy for metastatic colorectal cancer patients."

Lilly plans to present data from the RAISE trial at a scientific meeting in 2015 and expects to initiate regulatory submissions in the first half of 2015.

Gaynor said, "We now have four phase III ramucirumab trials that improved survival in three of the world's most common and deadly cancers—gastric, lung, and colorectal—supporting global regulatory submissions in multiple indications. The RAISE data also build on Lilly's growing presence in gastrointestinal cancer therapy."

Ramucirumab is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C and VEGF-D. VEGF Receptor 2 is an important mediator in the VEGF pathway. In an in vivo animal model, ramucirumab inhibited angiogenesis. Angiogenesis is a process by which new blood vessels form to supply blood to normal healthy tissues as well as tumors, enabling the cancer to grow.

Initiated in 2010, the study enrolled more than 1,000 patients across 26 countries. The primary endpoint (also referred to as the major efficacy outcome measure) of the RAISE trial was overall survival and key secondary endpoints (also referred to as the supportive efficacy outcome measures) included: progression-free survival; overall response rate; and safety.