The addition of ramucirumab to standard chemotherapy in a second-line setting extended survival for patients with advanced colorectal cancer, according to results of the randomized phase 3 RAISE study presented at the Gastrointestinal Cancers Symposium.
Ramucirumab (Cyramza, Eli Lilly) is an angiogenesis inhibitor that blocks the growth of new blood vessels to a tumor, starving it of nutrients. It is approved by the FDA for treatment of advanced gastric or gastroesophageal junction carcinoma, as well as non–small cell lung cancer. However, it is being studied in a variety of other malignancies.
“Colorectal cancer is the fourth most common cancer worldwide and, in the advanced setting, continues to be a highly lethal disease,” Josep Tabernero, MD, PhD, director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain, said during a press conference. “The RAISE trial clearly demonstrates that sustained inhibition of the angiogenesis pathway from first-line to second-line metastatic colorectal cancer improves survival in a clinically representative metastatic colorectal cancer population. Therefore, ramucirumab is an effective new treatment option for second-line treatment, including patients with poor prognosis.”
Tabernero and colleagues evaluated the addition of ramucirumab to second-line FOLFIRI chemotherapy, which consists of fluorouracil, leucovorin and irinotecan.
The analysis included 1,072 patients with metastatic colorectal cancer whose disease progressed on or after first-line treatment with bevacizumab (Avastin, Genentech) and standard chemotherapy. All patients had an ECOG performance status of 0 or 1, and all had adequate organ function.
Researchers randomly assigned 536 patients to ramucirumab 8 mg/kg intravenously plus FOLFIRI every 2 weeks. The other 536 patients received placebo plus FOLFIRI. Treatment continued until disease progression, unacceptable toxicity or death.
Baseline characteristics were similar between treatment arms.
OS served as the primary endpoint. PFS, objective response rate and safety served as secondary endpoints.
Tabernero and colleagues reported similar rates of tumor shrinkage (13.4% for ramucirumab; 12.5% for placebo) and objective response (13.4% for ramucirumab; 12.5% for placebo).
However, patients assigned ramucirumab demonstrated statistically significant improvements in PFS (5.7 months vs. 4.5 months; HR=0.79; 95% CI, 0.7-0.9) and OS (13.3 months vs. 11.7 months; HR=0.84; 95% CI, 0.73-0.98) compared with those assigned placebo.
Patients assigned ramucirumab experienced higher rates of grade ≥3 neutropenia (38.4% vs. 23.3%), hypertension (11.2% vs. 2.8%), diarrhea (10.8% vs. 9.7%) and fatigue (11.5% vs. 7.8%).
The occurrence of febrile neutropenia was similar between the two arms (3.6% vs. 2.7%).
“[This study] included patients with fast-growing tumors, so the findings are relevant to patients that we typically encounter in practice,” Tabernero said in a press release. “It is very encouraging that we now have another safe option that adds benefit to standard chemotherapy in this second-line setting.”
Although the study clearly demonstrated that the addition of ramucirumab to FOLFIRI provided a benefit, the findings should not be extrapolated to other chemotherapy regimens without formal investigation in clinical trials, researchers said. Future studies also should evaluate the effect of second-line ramucirumab in patients who underwent first-line treatment with the EGFR inhibitor cetuximab (Erbitux, ImClone), they said.
For more information:
Tabernero J. Abstract #512. Presented at: Gastrointestinal Cancers Symposium; Jan. 16-18, 2015; San Francisco.
Disclosure: The study was funded by Eli Lilly. The researchers report consultant/advisory roles with, honoraria from, research funding from, employment relationships with and stock ownership in AbbVie, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chugai Pharma, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Genentech, GlaxoSmithKline, ImClone Systems, Merck, Millennium Takeda, Novartis, Onyx, Pfizer, Roche, Sanofi, Taiho Pharmaceutical and Yakult.