The addition of the angiogenesis inhibitor ramucirumab to second-line FOLFIRI chemotherapy resulted in a significant delay in disease progression and prolongation of survival in patients with metastatic colorectal cancer who had previously progressed on first-line therapy.
“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,” said Josep Tabernero, MD, director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain. “Therefore, ramucirumab is an effective new treatment option for second-line treatment including patients with poor prognosis.”
Tabernero presented the results of the phase III study (abstract #512) at a press briefing ahead of the American Society of Clinical Oncology (ASCO) 2015 Gastrointestinal Cancers Symposium.
The study included 1,072 patients with metastatic disease that progressed during or after treatment with bevacizumab, oxaliplatin, and a fluoropyrimidine. The patients were randomly assigned to ramucirumab and FOLFIRI every 2 weeks per cycle (n = 536) or placebo plus FOLFIRI every 2 weeks per cycle (n = 536). The primary endpoint was overall survival.
The overall survival analysis showed that treatment with ramucirumab reduced the risk for death by 16% (hazard ratio [HR] = 0.84; P = .0219) and prolonged survival by a median of 1.6 months compared with FOLFIRI alone. Patients assigned ramucirumab plus FOLFIRI had a 13.3-month median survival compared with 11.7 months in the FOLFIRI arm.
In addition, ramucirumab reduced the risk of disease progression by 21% (HR = 0.79; P = .0005). The median progression-free survival was 5.7 months for patients assigned ramucirumab compared with 4.5 months for those assigned FOLFIRI alone.
According to Tabernero, there was a consistent treatment effect across all examined subgroups, including patients with KRAS mutant and wild-type tumors.
Patients on ramucirumab plus FOLFIRI had more grade 3/4 adverse events including neutropenia, fatigue, diarrhea, and hypertension; however, the rate of febrile neutropenia was similar between the two treatment arms.
Commenting on these results, press briefing moderator Smitha S. Krishnamurthi, MD, of Case Western Reserve University, said, “We now know that when patients with advanced colorectal cancer have progression of disease on first-line chemotherapy plus bevacizumab we can either continue bevacizumab with second-line chemotherapy or use a different angiogenesis inhibitor, aflibercept, with chemotherapy and now we know ramucirumab can be given with chemotherapy in this setting.”