Eli Lilly and Company has announced that the European Commission has granted marketing authorisation for ramucirumab (Cyramza®).
Ramucirumab is the first licensed therapy specifically indicated for adult patients with advanced gastric (stomach) or gastro-oesophageal junction adenocarcinoma (GOJ), following prior chemotherapy (fluoropyrimidine and platinum). Ramucirumab is approved in combination with paclitaxel chemotherapy and as a single agent in patients for whom treatment with paclitaxel is not appropriate. Ramucirumab's approval is based on two international Phase III studies, showing it extended overall survival time and delayed disease progression versus each study comparator. [i],[ii],[iii]
"Unfortunately, most patients with gastric cancer face a poor prognosis. Around 80% are first diagnosed once their cancer has spread and become difficult to treat. Despite research efforts, there have been few advances in the last 30 years and inoperable gastric cancer remains a devastating disease. Ramucirumab provides a welcome new treatment option for these patients," says Professor David Ferry, Global Senior Medical Director, Lilly Oncology and previous Professor of Medical Oncology, New Cross Hospital, Wolverhampton, UK
Ramucirumab's Phase III study programme involved 1,020 patients from 289 cancer centres. Results from the RAINBOW study showed that ramucirumab, combined with paclitaxel, significantly extended overall survival time to 9.6 months compared with 7.4 months for placebo plus paclitaxel (hazard ratio [HR] 0.807 [95% CI 0.678-0.962]; p=0.017).[ii]
As a single agent in the REGARD study, results showed ramucirumab extended overall survival time to 5.2 months compared with 3.8 months for best supportive care (HR 0.776, 95% CI 0.603-0.998; p=0.047).[iii] In both studies, ramucirumab was shown to delay disease progression and improve objective response rate ie tumour shrinkage.[ii],[iii]
In the combination study, the most common adverse events of grade 3 or higher for ramucirmab plus paclitaxel versus placebo plus paclitaxel were neutropenia (41% vs 19%), leucopenia (17% vs 7%), hypertension (14% vs 2%), fatigue (12% vs 5%), anaemia (9% vs 10%) and abdominal pain (6% vs 3%). In the single agent study, adverse events were mostly similar between the ramucirumab and placebo groups, although rates of hypertension were higher (16% vs 8%).
'Lilly is proud to have developed the first licensed therapy specifically indicated for second-line advanced stomach cancer and gastro-oesophageal junction adenocarcinoma. Today marks an important milestone for patients with this difficult-to-treat disease. Ramucirumab is an innovative therapy that specifically binds to and blocks vascular endothelial growth factor (VEGF) Receptor 2 - a key mediator of VEGF-induced angiogenesis, which feeds cancer growth. Ramucirumab's development is testament to our commitment to support people living with cancer and those who care for them' said Richard Gaynor, M.D., Senior Vice President, Product Development and Medical Affairs for Lilly Oncology.
Ramucirumab was granted Orphan Drug Designation by the European Commission for treatment of gastric cancer in the EU. Orphan drug status is designated to medicines for the treatment of rare diseases, where available options are limited or where a medicine offers significant benefit over existing treatments.
About the RAINBOW Trial
RAINBOW was a global, randomized, double-blinded, placebo-controlled Phase III study of ramucirumab plus paclitaxel compared to placebo plus paclitaxel as a treatment in patients with advanced (locally advanced, unresectable or metastatic) gastric cancer including gastro-oesophageal junction adenocarcinoma refractory to or progressive after initial fluoropyrimidine- and platinum-containing chemotherapy. In total, 665 patients were randomized in 27 countries. The major efficacy outcome measure (i.e., primary endpoint) of the RAINBOW trial was overall survival and supportive efficacy outcome measure (i.e., secondary endpoint) was progression-free survival.
About the REGARD Trial
REGARD was a global, randomized, double-blinded, placebo-controlled Phase III study of ramucirumab plus best supportive care (BSC) compared to placebo plus BSC as a treatment in patients with locally advanced or metastatic gastric cancer including GOJ adenocarcinoma following progression after initial fluoropyrimidine- or platinum-containing chemotherapy. In total, 355 patients were randomized in 29 countries. The major efficacy outcome measure of the REGARD trial was overall survival and the supportive efficacy outcome measure was progression-free survival.
About Gastric Cancer
Gastric cancer is a leading cause of cancer death, killing almost 100 people in the UK every week. [iv] It is the fifth most common cancer in the world but is more prevalent outside of the EU and the US.[v] Gastric cancer is a disease in which cancer cells form in the stomach lining. It 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.[vi] The most common type of stomach cancer (95%) is called adenocarcinoma, which starts in gland cells in the innermost stomach lining.[vi] Gastro-oesophageal junction (GOJ) cancer occurs where the oesophagus meets the stomach - this cancer is on the rise, probably due to an increase in obesity and reflux disorders.[vii]
About Ramucirumab
Ramucirumab is the first biological therapy for use in advanced gastric cancer, which specifically binds to vascular endothelial growth factor (VEGF) Receptor 2 - a key mediator of VEGF-induced angiogenesis. Angiogenesis involves the formation of new blood vessels that feed tumours and enable their growth and spread.[viii] Elevated levels of VEGF are associated with tumour aggressiveness and poorer survival.[ii] By binding to VEGFR-2, ramucirumab blocks VEGFR ligands - VEGF-A, VEGF-C and VEGF-D8 - to stop signals from the tumour directing new vessel growth, thereby starving the tumour of nutrients and oxygen.