INDIANAPOLIS—Eli Lilly and Company today announced that the RAISE trial, a Phase 3 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, 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 in a statement to the press. "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.
Dr. Gaynor added, "We now have four Phase 3 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.
RAISE is a global, randomized, double-blind Phase 3 study of ramucirumab plus FOLFIRI (irinotecan, folinic acid and 5-fluorouracil) compared to placebo and FOLFIRI as a second-line treatment in patients with mCRC who have progressed on or after first-line treatment with bevacizumab, oxaliplatin and a fluoropyrimidine. Of the approximate 33,000 patients currently being treated in the second-line mCRC setting in the U.S., roughly one-third would have been eligible for the RAISE trial based on this first-line treatment.
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.
Colorectal cancer (CRC) is the fourth leading cause of cancer death worldwide, killing nearly 700,000 people in 2012. Only lung, liver, and stomach cancers caused more cancer-related deaths. In 2012, the global incidence of CRC is estimated to be over 1.3 million. CRC is the second leading cause of cancer death in the U.S.
Metastatic CRC occurs when the disease has spread to at least one distant organ, such as the liver, lungs, or lining of the abdomen. One out of five CRC patients is diagnosed with metastatic disease. The five-year survival rate for patients with mCRC is 11.7 percent.
Angiogenesis involves the migration, growth, and differentiation of endothelial cells, which line the inside wall of blood vessels. Chemical signals in the body stimulate the repair of damaged blood vessels and formation of new blood vessels during this process. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread.
Some tumors create proteins called VEGF. These proteins attach to the VEGF receptors of blood vessel cells causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to the blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.
Ramucirumab, marketed as CYRAMZA, is approved for use as a single agent in the U.S. for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have progressed after prior fluoropyrimidine- or platinum-containing chemotherapy. CYRAMZA inhibited angiogenesis in an in-vivo animal model. CYRAMZA is a VEGF Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 and blocks binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.
There are several studies underway or planned to investigate CYRAMZA as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.
Source: Eli Lilly and Company
