Date: 2015-06-19
Type of
information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The Lancet Oncology
Company: Eli Lilly (USA - IN)
Product: Cyramza® (ramucirumab)
Action
mechanism:
- monoclonal antibody. Cyramza® (ramucirumab) is an antiangiogenic therapy. This vascular endothelial growth factor (VEGF) Receptor 2 antagonist specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D.
- Ramucirumab has been granted Orphan Drug Designation for treatment of hepatocellular carcinoma in the U.S. and EU. Orphan drug status is given - in the U.S. by the FDA's Office of Orphan Products Development (OOPD) and in the EU by the European Commission - to medicines that have demonstrated promise for the treatment of rare diseases.
Disease: patients with hepatocellular carcinoma who have been previously treated with sorafenib in the first-line setting
Therapeutic
area: Cancer - Oncology
Country: Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Republic of Korea, Netherlands, Norway, Philippines, Portugal, Romania, Spain, Sweden, Switzerland, Taiwan, Thailand, USA
Trial
details:
- REACH is a global, randomized, double-blind Phase III study of ramucirumab plus best supportive care compared to placebo plus best supportive care as a second-line treatment in patients with hepatocellular carcinoma who have been previously treated with sorafenib in the first-line setting. Initiated in 2010, the study enrolled 565 patients across 27 countries; as defined in the trial protocol, the primary analyses are focused on patients with a Child-Pugh score of < 7 (Child-Pugh Class A only). The primary endpoint (also referred to as the major efficacy outcome measure) of the REACH trial was overall survival and key secondary endpoints (also referred to as the supportive efficacy outcome measures) include: progression-free survival; overall response rate; time to progression; and safety. (NCT01140347)
Latest
news:
- • On June 19, 2015, Eli Lilly announced that The Lancet Oncology has published results of the Phase III REACH trial that evaluated Cyramza® (ramucirumab) as a second-line treatment for people with hepatocellular carcinoma (HCC). While the REACH trial's primary endpoint of overall survival favored the Cyramza® arm, it was not statistically significant. However, encouraging single-agent Cyramza® activity was observed, with meaningful improvements in key secondary endpoints as well as within certain patient subgroups. The global, randomized, double-blind REACH trial compared ramucirumab plus best supportive care to placebo plus best supportive care as a second-line treatment in patients with HCC after being treated with sorafenib in the first-line setting. Median overall survival (OS) was 9.2 months on the ramucirumab arm compared to 7.6 months on the placebo arm (HR 0.866; 95% CI: 0.717-1.046; p=0.1391). While the median OS was not statistically significant, a prespecified subgroup of patients with an elevated baseline of alpha-fetoprotein (AFP) ?400 ng/mL showed a greater survival improvement with ramucirumab treatment. Median OS in this subgroup of patients was 7.8 months in the ramucirumab arm compared to 4.2 months in the placebo arm (HR 0.674; 95% CI 0.508-0.895; p=0.0059).
- The REACH study analyses presented at the Gastrointestinal Cancers Symposium earlier this year concluded that a greater reduction in the risk of death in patients with progressively higher baseline AFP values warrants further investigation. Based on these findings, Lilly will soon begin enrollment in REACH-2, a new Phase III trial to evaluate the benefit of ramucirumab treatment in advanced liver cancer patients with an elevated baseline AFP (NCT02435433).
- The safety data in the REACH study were consistent with results from previous single-agent ramucirumab studies and the safety information included in the U.S. Prescribing Information for ramucirumab. The most common (?5% incidence) clinical grade ?3 adverse events occurring more frequently in patients on the ramucirumab arm compared to the control arm were hypertension (12% vs. 4%), asthenia (fatigue) (5% vs. 2%), and malignant neoplasm progression (6% vs. 4%). The safety profile of ramucirumab in patients with elevated baseline AFP > 400 ng/mL was consistent with that observed in the overall safety population.
Is
general: Yes
