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The combination of ramucirumab and FOLFIRI significantly improved OS and PFS compared with chemotherapy alone as a second-line treatment for patients with mCRC.
Richard Gaynor, MD
The combination of ramucirumab (Cyramza) and FOLFIRI significantly improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone as a second-line treatment for patients with metastatic colorectal cancer (mCRC), according to early findings from the phase III RAISE study.
In the RAISE study, patients were randomized to ramucirumab at 8 mg/kg every 2 weeks plus FOLFIRI or FOLFIRI plus placebo. The primary endpoint was OS, with secondary outcome measures focused on PFS and overall response rate (ORR). The study enrolled patients with mCRC who progressed on frontline treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine.
The most common grade 3/4 adverse events with ramucirumab in patients with mCRC were neutropenia fatigue, hypertension, and diarrhea. In previous studies, the rate of grade 3/4 side effects with single-agent ramucirumab in advanced gastric cancer versus placebo were hypertension (8% vs 3%), diarrhea (1% vs 2%), and hyponatremia (3% vs 1%).
Eli Lilly and Company, the company developing the drug, announced plans to present data from the RAISE trial in 2015. Additionally, the company expects to initiate regulatory submissions in the first half of 2015.
"Patients with metastatic colorectal cancer — particularly those in the second-line setting — continue to need new treatment options that improve survival," Richard Gaynor, MD, senior vice president, product development and medical affairs for Lilly Oncology, said in a press release. "We are pleased that the RAISE study demonstrated a survival benefit and are hopeful that ramucirumab will become a new anti-angiogenic treatment option after first-line bevacizumab-containing therapy for metastatic colorectal cancer patients."
The VEGFR-2 inhibitor ramucirumab has been explored across a variety of settings, including gastric cancer and non-small cell lung cancer (NSCLC). In April 2014, ramucirumab was approved as a treatment for patients with unresectable gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma following fluoropyrimidine- or platinum-containing therapy. This approval was based on a 1.4-month extension in OS experienced by patients enrolled in the phase III REGARD study.
According to results published in The Lancet, the median OS with ramucirumab in the REGARD trial was 5.2 months compared with 3.8 months with placebo (HR = 0.776; 95% CI, 0.603-0.998; P = 0.047). The median PFS with ramucirumab was 2.1 versus 1.3 months with placebo (HR = 0.483; 95% CI, 0.376-0.620; P < 0.0001).
Results from the RAINBOW trial, which combined ramucirumab with paclitaxel, demonstrated further benefit for the drug in patients with gastric cancer, according to results presented at the 2014 Gastrointestinal Cancers Symposium. In this study, the median OS with ramucirumab was 9.7 versus 7.4 months for paclitaxel alone (HR = 0.807; 95% CI, 0.678-0.962; P = .0169). The median PFS was 4.4 months with ramucirumab compared with 2.9 months for docetaxel (HR = 0.635; 95% CI, 0.536-0.752; P < .0001).
For patients with NSCLC, data from the phase III REVEL trial demonstrated a 1.4-month improvement in OS with the combination of ramucirumab and docetaxel compared with docetaxel plus placebo. Data from this analysis were presented at the 2014 ASCO Annual Meeting.
In the study, the median OS with ramucirumab was 10.5 versus 9.1 months with placebo (HR = 0.857; 95% CI, 0.751-0.98; P = .0235). Median PFS was 4.5 versus 3 months, for the ramucirumab combination and docetaxel, respectively (HR = 0.762; P <.0001). These findings will be the basis for a regulatory submission for ramucirumab in NSCLC, which is expected later this year.
"We now have four phase III ramucirumab trials that improved survival in three of the world's most common and deadly cancers — gastric, lung, and colorectal supporting global regulatory submissions in multiple indications," Gaynor said in a release. "The RAISE data also build on Lilly's growing presence in gastrointestinal cancer therapy."