The FDA ( Food and Drug Administration ) has approved Ramucirumab ( Cyramza ) 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.
Now, Cyramza is approved both as a single-agent treatment and in combination with chemotherapy.
This FDA approval for Cyramza is based on the phase III RAINBOW trial, which compared Cyramza plus Paclitaxel to placebo plus Paclitaxel.
Efficacy endpoints in the trial included the major efficacy outcome measure of overall survival and the supportive efficacy outcome measures of progression-free survival and objective response rate.
The labeling for Cyramza contains a Boxed Warning regarding increased risk of hemorrhage, including severe and sometimes fatal hemorrhagic events.
Cyramza should be permanently discontinued in patients who experience severe bleeding.
Ramucirumab is an antiangiogenic therapy. It is a vascular endothelial growth factor ( VEGF ) Receptor 2 antagonist that specifically binds and blocks activation of VEGFR-2, by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.
RAINBOW was a multinational, randomized, double-blinded, placebo-controlled fhase III study of Ramucirumab plus Paclitaxel compared to placebo plus Paclitaxel in people with locally advanced or metastatic gastric or gastroesophageal junction ( GEJ ) adenocarcinoma, whose cancer had progressed after fluoropyrimidine- and Platinum-containing chemotherapy.
Initiated in 2010, the global study randomized a total of 665 patients across 27 countries in North America, South America, Europe, Australia and Asia.
RAINBOW is the first phase III study to demonstrate a survival benefit with a biologic used in combination with chemotherapy in this setting.
Ramucirumab plus Paclitaxel significantly extended median overall survival compared with placebo plus Paclitaxel ( 9.6 months [ 95% confidence interval (CI): 8.5, 10.8 ] vs 7.4 months [ 95% CI: 6.3, 8.4 ], respectively; hazard ratio, HR=0.81 [ 95% CI: 0.68, 0.96 ]; P=0.017 ).
Furthermore, Ramucirumab plus paclitaxel significantly delayed disease progression ( progression-free survival of 4.4 months for Ramucirumab plus Paclitaxel [ 95% CI: 4.2, 5.3 ] ) vs 2.9 months for placebo plus Paclitaxel [ 95% CI: 2.8, 3.0 ]; HR=0.64 [ 95% CI: 0.54, 0.75 ]; P less than 0.001 ).
Significantly more patients responded to Ramucirumab combined with Paclitaxel than with Paclitaxel alone ( 28% [ 95% CI: 23, 33 ] for Ramucirumab plus paclitaxel vs 16% [ 95% CI: 13, 20 ] for placebo plus Paclitaxel; P less than 0.001 ).
The percentage of deaths at the time of analysis was 78% ( 256 patients ) and 78% ( 260 patients ) in the Ramucirumab-plus-Paclitaxel and placebo-plus-Paclitaxel treatment arms, respectively.
The progression-free survival number of events was 279 ( 85% ) and 296 ( 88% ) for the Ramucirumab-plus-Paclitaxel and placebo-plus-Paclitaxel treatment arms, respectively.
RAINBOW trial, the most common adverse reactions ( all grades ) observed in patients treated with Ramucirumab plus Paclitaxel at a rate of greater than or equal to 30% and greater than or equal to 2% higher than placebo plus Paclitaxel were fatigue ( 57% vs 44% ), neutropenia ( 54% vs 31% ), diarrhea ( 32% vs 23% ), and epistaxis ( 31% vs 7% ).
The most common serious adverse events with Ramucirumab plus Paclitaxel in the RAINBOW trial were neutropenia ( 3.7% ) and febrile neutropenia ( fever and potentially other infection signs along with low white blood cell count ) ( 2.4% ); 19% of patients treated with Ramucirumab plus Paclitaxel received granulocyte colony-stimulating factors.
Gastric cancer is the fifth most common cancer in the world and is the third-leading cause of cancer death. There were nearly one million new cases worldwide in 2012 ( 631,000 men, 320,000 women ) with approximately 723,000 deaths ( 469,000 men, 254,000 women ).
Stomach cancer is more prevalent in countries outside the U.S. and EU. In the U.S., it is estimated that approximately 22,000 people will be diagnosed with gastric cancer in 2014.
Gastric cancer develops slowly, usually over many years, and often goes undetected. As stomach cancer advances, it can travel through the bloodstream and spread to organs such as the liver, lungs and bones.
The most common type of stomach cancer is called adenocarcinoma, which starts from one of the common cell types found in the lining of the stomach. ( Xagena )
Source: Eli Lilly, 2014