Cyramza® (ramucirumab): RAISE - Varför FOLFIRI som kontrollarm?

Information from Summary of Product Characteristics

Cyramza, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin and a fluoropyrimidine.¹

Study Design

The RAISE trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated FOLFIRI and ramucirumab vs FOLFIRI and placebo in the second-line treatment of patients with mCRC who had progressed on first-line combination therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Patients were randomly assigned in a 1:1 ratio (stratified by region, KRAS mutation status, and time to progressive disease after beginning first-line treatment) to receive IV infusions of either FOLFIRI plus ramucirumab 8 mg/kg (n=536) or FOLFIRI plus placebo (n=536) once every 2 weeks.²

Rationale for FOLFIRI Control Arm

When the RAISE trial was initiated, FOLFIRI was selected as the control arm because at that time

• oxaliplatin- and irinotecan-based treatments were considered equally effective and interchangeable for the first- and second-line treatment of mCRC

• FOLFIRI was a globally-accepted standard of care in the second-line setting after progression on an oxaliplatin-based first-line treatment regimen, and

• there was no standard combination of targeted therapy plus FOLFIRI after progression on an oxaliplatin plus bevacizumab regimen.^3,4

References

1. Cyramza [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508. http://dx.doi.org/10.1016/S1470-2045(15)70127-0

3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Colon Cancer (version 2.2015, 03Oct2014). http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 22Dec2014.

4. Van Cutsem E, Cervantes A, Nordlinger B, Arnold D on behalf of the ESMO Guidelines Working Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3):iii1-iii9. http://dx.doi.org/10.1093/annonc/mdu260. Accessed 22Dec2014.

Glossary

FOLFIRI = irinotecan, folinic acid, and 5-fluorouracil

IV = intravenous

KRAS = Kirsten rat sarcoma virus 

mCRC = metastatic colorectal cancer