Ramucirumab Approved for Advanced Stomach Cancer

Debbie Zelman

The FDA has approved ramucirumab (Cyramza) as a single-agent treatment for patients with unresectable or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma following fluoropyrimidine- or platinum-containing therapy.

Ramucirumab is the first biologic agent approved for the treatment of patients with gastric and GEJ cancer based on a significant increase in overall survival (OS) in the phase III REGARD trial. Treatment with the angiogenesis inhibitor resulted in a median OS of 5.2 months compared with 3.8 months with placebo. The median progression-free survival (PFS) was 2.1 months compared with 1.3 months, for ramucirumab and placebo, respectively.

“As someone who has experienced firsthand the limited options available to treat this devastating disease, I consider this approval to be much needed,” Debbie Zelman, president and founder of a leading international patient advocacy organization, Debbie’s Dream Foundation, said in a release. “This is a significant moment for many patients and their families.”

In the REGARD study, 355 patients with advanced gastric cancer or GEJ adenocarcinoma were randomized 2:1 to receive best supportive care plus either ramucirumab (n=238) or placebo (n=117). Ramucirumab was administered intravenously every 2 weeks at 8 mg/kg for a median duration of 8 weeks. The primary endpoint was OS, with secondary endpoints of PFS, overall response rate (ORR), and safety.

According to results published in The Lancet, the hazard ratio (HR) for OS was 0.776 (5.2 months versus 3.8 months; 95% CI, 0.603-0.998; P = 0.047) and the HR for PFS was 0.483 (9.7 months versus 7.4 months; 95% CI, 0.376-0.620; P < 0.0001). ORR was 3.4% for ramucirumab and 2.6% for placebo, and disease control rates were 48.7% and 23.1%, respectively.

Approximately 75% of patients in the ramucirumab arm were diagnosed with advanced gastric cancer. Following the discontinuation of treatment, 32% of patients in the ramucirumab arm went on to receive chemotherapy compared with approximately 39% of those on placebo.

Ramucirumab was approved with a Boxed Warning regarding increased risk of severe and sometimes fatal hemorrhage. In the study, hypertension was more common in the ramucirumab arm (16% versus 8%). However, all-grade adverse events were similar between the two groups at 94% compared with 88% for ramucirumab and placebo, respectively.

The most common serious adverse events with ramucirumab were anemia (3.8%) and intestinal obstruction (2.1%). According to laboratory assessments, 8% of ramucirumab-treated patients developed proteinuria versus 3% in the placebo arm. Moreover, 2 patients discontinued ramucirumab due to proteinuria.

“There is a high unmet medical need in patients with this disease,” Charles Fuchs, MD, MPH, director of the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute and lead investigator of the REGARD trial, said in a statement. “This approval represents a meaningful advance for patients and gives those of us who treat them an important new second-line treatment option.”

Ramucirumab is being explored in a number of phase III clinical trials, including studies in colorectal cancer, non-small cell lung cancer, and hepatocellular carcinoma. In February, Eli Lilly and Company, the developer of ramucirumab, announced that treatment with the drug in combination with docetaxel extended OS and PFS in patients with NSCLC in the phase III REVEL study. Results from this investigation will be presented later this year and will likely be submitted for regulatory approval.