Second-line ramucirumab may prolong life in colorectal cancer

Last Updated: 2015-01-13

By Megan Brooks

NEW YORK (Reuters Health) - When metastatic colorectal cancer progresses after first-line combination chemotherapy, adding the angiogenesis inhibitor ramucirumab (Cyramza, Eli Lilly) to standard second-line chemotherapy can delay disease progression and prolong life, according to new findings from the phase 3 RAISE study.

"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," Dr. Josep Tabernero, director of the Vall d'Hebron Institute of Oncology in Barcelona, Spain said during a media briefing Monday.

"Therefore, ramucirumab is an effective new treatment option for second-line treatment, including patients with poor prognosis," he added.

Dr. Tabernero will present the data later this week at the 2015 Gastrointestinal Cancers Symposium in San Francisco.

Ramucirumab is a vascular endothelial growth-factor receptor-2 (VEGFR) antagonist. RAISE was a randomized, double-blind, multicenter phase 3 study of irinotecan, folinic acid and 5-FU (FOLFIRI) plus ramucirumab or placebo in 1072 patients with metastatic colorectal cancer that progressed during or following first-line treatment with a combination of bevacizumab, oxaliplatin and a fluoropyrimidine.

Patients were randomized 1:1 to ramucirumab 8 mg/kg plus FOLFIRI or placebo plus FOLFIRI every two weeks per cycle until disease progression or unacceptable toxicity.

Ramucirumab led to a statistically significant improvement in both progression-free and overall survival, Dr. Tabernero reported.

The median time to disease progression was 5.7 months in the ramucirumab group vs 4.5 months in the placebo group. With ramucirumab, the risk of progression decreased by 21% (hazard ratio 0.79, p=0.0005).

The median overall survival was 13.3 months with ramucirumab vs 11.7 months with placebo. Adding ramucirumab reduced the risk of death by 16% (hazard ratio 0.84, p=0.0219).

"There was a consistent treatment effect across all different subgroups," Dr. Tabernero noted.

More grade 3 and 4 adverse events occurred with ramucirumab + FOLFIRI, including neutropenia, fatigue, diarrhea and hypertension.

"However, the rate of febrile neutropenia, the clinically significant toxicity, was similar between the two arms," Dr. Tabernero noted. Ramucirumab + FOLFIRI was "well tolerated, and overall, the adverse events were manageable," he added.

Briefing moderator Dr. Smitha Krishnamurthi, of the American Society of Clinical Oncology (ASCO) symposium news planning team and Case Western Reserve University in Cleveland, Ohio, said, "It's always exciting to have a new active drug for our patients. We now know that when patients with advanced colorectal cancer have progression of their disease on first-line chemotherapy plus bevacizumab, we can either continue the bevacizumab with second-line chemotherapy or use a different angiogenesis inhibitor, aflibercept, with chemotherapy. And now we know that ramucirumab can be given with chemotherapy in this setting. All of these approaches have had a similar increase in survival. It will be interesting to see the effects of ramucirumab in other randomized studies and settings for colorectal cancer."

The 2015 Gastrointestinal Cancers Symposium is co-sponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society for Surgical Oncology.

The RAISE study was funded by Eli Lilly. Three investigators are employees of the company and most of the other investigators have financial relationships with the company.