Eli Lilly and Company has received its third US Food and Drug Administration (FDA) approval for Cyramza (ramucirumab).
Specifically, Cyramza is now also indicated in combination with docetaxel, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Cyramza. This latest approval of Cyramza was received on December 12, 2014.
This approval of Cyramza (ramucirumab injection 10 mg/mL solution) marks the first FDA-approved medicine for use in combination with docetaxel in the second-line treatment of metastatic NSCLC, including nonsquamous and squamous histologies.
"Lilly is determined to meet the challenge of delivering new treatments for people with difficult-to-treat cancers, such as non-small cell lung cancer," said Sue Mahony, senior vice president and president, Lilly Oncology. "We are pleased with this approval and excited for the therapeutic advantage that Cyramza in combination with docetaxel can bring to second-line, metastatic NSCLC patients. It truly builds on Lilly's continued commitment to discovering potential treatment options for people fighting lung cancer."
The REVEL phase III trial compared Cyramza plus docetaxel to placebo plus docetaxel, and included people with nonsquamous and squamous forms of NSCLC. 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.
Lung cancer is the leading cause of cancer death in the US and most other countries, and NSCLC accounts for about 85 percent of all lung cancer cases. Approximately half of patients with metastatic NSCLC who begin first-line therapy will move on to second-line treatment.v Despite currently available therapies, there continues to be a need for new second-line treatment options for patients with NSCLC.
Lilly is committed to offering patient assistance programmes for eligible patients receiving Cyramza treatment.
Cyramza (ramucirumab) is approved in combination with docetaxel (a type of chemotherapy) as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy; it is also approved as a single agent or in combination with paclitaxel (a type of chemotherapy) as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Cyramza is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Cyramza inhibited angiogenesis in an in vivo animal model.
Angiogenesis is the process of making new blood vessels. In a person with cancer, angiogenesis creates new blood vessels that give a tumour its own blood supply, allowing it to grow and spread.
Some tumours 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 tumours. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumour angiogenesis.
REVEL was a global, randomised, double-blinded phase III study of Cyramza plus docetaxel compared to placebo plus docetaxel in people with metastatic NSCLC whose cancer had progressed on or after prior platinum-based chemotherapy for locally advanced or metastatic disease. In total, 1,253 patients - including people with nonsquamous (73 per cent) and squamous (26 per cent) forms of NSCLC - were randomised in 26 countries over six continents. REVEL is the first positive phase III study of a biologic in combination with chemotherapy to demonstrate improved overall survival compared to chemotherapy alone in second-line metastatic NSCLC.
In the trial, Cyramza plus docetaxel achieved a statistically significant improvement in overall survival (the primary endpoint), progression-free survival and objective response rate (secondary endpoints). Cyramza plus docetaxel significantly extended median overall survival compared to placebo plus docetaxel (10.5 months [95 per cent confidence interval (CI): 9.5, 11.2] vs. 9.1 months [95 per cent CI: 8.4, 10.0], respectively; hazard ratio 0.86 [95 per cent CI: 0.75, 0.98]; P=0.024). Furthermore, Cyramza plus docetaxel significantly delayed disease progression (progression-free survival of 4.5 months for CYRAMZA plus docetaxel [95 per cent CI: 4.2, 5.4] vs. 3.0 months for placebo plus docetaxel [95 per cent CI: 2.8, 3.9]; hazard ratio 0.76 [95 per cent CI: 0.68, 0.86]; P < 0.001). The percentage of deaths at the time of analysis was 68 per cent (428 patients) and 73 per cent (456 patients) in the Cyramza-plus-docetaxel and placebo-plus-docetaxel arms, respectively. The progression-free survival number of events was 558 (89 per cent) and 583 (93 per cent) for Cyramza-plus-docetaxel and placebo-plus-docetaxel treatment arms, respectively. Significantly more patients responded to Cyramza combined with docetaxel than with placebo plus docetaxel (23 per cent [95 per cent CI: 20, 26] for Cyramza plus docetaxel vs. 14 per cent [95 per cent CI: 11, 17] for placebo plus docetaxel; P < 0.001).
The labelling for Cyramza contains a Boxed Warning for hemorrhage and additional Warnings and Precautions for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforations, impaired wound healing, clinical deterioration in patients with Child-Pugh B or C cirrhosis, and reversible posterior leukoencephalopathy syndrome. In the REVEL trial, the most common adverse reactions (all grades) observed in patients treated with Cyramza plus docetaxel at a rate of =30 per cent and =2 per cent higher than placebo were neutropenia (low white blood cell count) (55 per cent vs. 46 per cent), fatigue/asthenia (weakness) (55 per cent vs. 50 per cent) and stomatitis/mucosal inflammation (37 per cent vs. 19 per cent). The most common serious adverse events with CYRAMZA were febrile neutropenia (fever and potentially other infection signs along with low white blood cell count) (14 per cent), pneumonia (6 per cent), and neutropenia (5 per cent); 42 per cent of patients treated with CYRAMZA plus docetaxel received granulocyte colony-stimulating factors (treatment for low white blood cells) vs. 37 per cent of patients who received placebo plus docetaxel.
Lung cancer is the leading cause of cancer death in the US and most other countries, killing nearly 1.6 million people worldwide each year. In the US, lung cancer is responsible for approximately 27 per cent of all cancer deaths, more than those from breast, colon and prostate cancers combined. Stage IV NSCLC is a very difficult-to-treat cancer and the prognosis is poor for metastatic NSCLC.vi NSCLC is much more common than other types of lung cancer, and accounts for about 85 per cent of all lung cancer cases. For those people affected by NSCLC, about 70 per cent have nonsquamous cell carcinoma, while about 30 per cent have squamous cell carcinoma. Approximately half of patients with metastatic NSCLC who begin first-line therapy will move on to second-line treatment.v Despite currently available therapies, there continues to be a need for new second-line treatment options for patients with NSCLC.
The Lilly PatientOne program addresses financial and coverage issues for qualified uninsured, underinsured and insured patients who are prescribed a Lilly Oncology product. Lilly PatientOne provides reimbursement assistance for eligible patients who are prescribed a Lilly Oncology product, such as information about coding and billing, prior authorisation, benefits investigation, and denied claim appeals, as well as operating a patient assistance programme.
Cyramza (ramucirumab) is used with a chemotherapy called docetaxel to treat metastatic non-small cell lung cancer (NSCLC) in patients whose cancer has progressed on or after being treated with other initial types of chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Cyramza.
Cyramza is also approved as a single agent or in combination with paclitaxel (a type of chemotherapy) as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.