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Cyramza (Ramucirumab) Receives Fourth FDA Approval
Cyramza (ramucirumab injection 10 mg/mL solution, Eli Lilly) has received its fourth FDA approval. The drug is now indicated in combination with Folfiri (irinotecan, folinic acid, and 5-fluorouracil) chemotherapy for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
The approval was based on results from the phase III RAISE trial, which compared ramucirumab plus Folfiri with placebo plus Folfiri in people with mCRC who had disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Efficacy endpoints included the major efficacy outcome measure of overall survival (OS) and the supportive efficacy outcome measure of progression-free survival (PFS). The patients were randomly assigned to receive ramucirumab plus Folfiri (n = 536) or placebo plus Folfiri (n = 536) every 2 weeks.
Patients treated with the ramucirumab/Folfiri combination achieved a median OS of 13.3 months compared with 11.7 months for those treated with placebo/Folfiri –– a statistically significant improvement that reduced the risk of death by 15% (hazard ratio [HR], 0.85; P = 0.023). The death rates at the time of the analysis were 69% (372 patients) and 74% (397 patients) in the ramucirumab/Folfiri and placebo/Folfiri treatment arms, respectively.
The ramucirumab/Folfiri combination also demonstrated a statistically significant improvement in the secondary endpoint of PFS compared with the placebo/Folfiri arm, with a median PFS of 5.7 months versus 4.5 months, respectively (HR, 0.79; P < 0.001). The event rates at the time of the analysis were 89% (476 patients) and 92% (494 patients) in the ramucirumab/Folfiri and placebo/Folfiri arms, respectively.
In the U.S., ramucirumab is approved for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in combination with docetaxel as a treatment for people with metastatic non–small-cell lung cancer whose cancer has progressed on or after platinum-based chemotherapy. In addition, ramucirumab is approved with Folfiri as a therapy for people with mCRC whose cancer has progressed on or after treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine.
Some tumors create vascular endothelial growth factor (VEGF) proteins. These proteins attach to VEGF receptors on blood-vessel cells, causing new blood vessels to form around the tumors and enabling growth. Blocking VEGF proteins from linking to 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 (VEGFR-2) is linked most closely to VEGF-induced tumor angiogenesis.
Ramucirumab is an antiangiogenic therapy. It is a vascular endothelial VEGFR-2 antagonist that specifically binds and blocks activation of VEGFR-2 by blocking the binding of VEGF receptor ligands VEGF-A, -C, and -D. Ramucirumab inhibited angiogenesis in an in vivo animal model.
The labeling for Cyramza (ramucirumab) contains boxed warnings for hemorrhage, gastrointestinal perforation, and impaired wound healing as well as additional warnings and precautions for arterial thromboembolic events, hypertension, infusion-related reactions, clinical deterioration in patients with Child-Pugh B or C cirrhosis, reversible posterior leukoencephalopathy syndrome, proteinuria (including nephrotic syndrome), thyroid dysfunction, and embryofetal toxicity.
The most common adverse events (AEs) observed in the ramucirumab/Folfiri-treated patients compared with the placebo/Folfiri group included diarrhea (60% vs. 51%, respectively), neutropenia (59% vs. 46%), decreased appetite (37% vs. 27%), epistaxis (33% vs. 15%), and stomatitis (31% vs. 21%). The most common serious AEs with ramucirumab plus Folfiri included diarrhea (3.6%), intestinal obstruction (3.0%), and febrile neutropenia (2.8%).
Despite advances in treating CRC in recent years, the mortality rate remains significant. CRC is the second leading cause of cancer death in the U.S. and the fourth leading cause of cancer death worldwide, killing nearly 700,000 people in 2012. The global incidence of CRC is estimated to be more than 1.3 million. Approximately one out of five CRC patients is diagnosed with metastatic disease, and the 5-year survival rate for these patients is 12.9%.
Source: Eli Lilly; April 24, 2015.