ASCO Gastrointestinal Cancers Symposium 2015
ASCO GICS 2015. Abstract 512. RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp).
Presenter: Josep Tabernero
Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI.
Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3 months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in >5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3%), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%).
Conclusion: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified.
CARE Faculty Canadian Perspective:
RAISE is a randomized phase III clinical trial that evaluated the efficacy and safety of the addition of ramucirumab to FOLFIRI chemotherapy in the second-line treatment of metastatic colorectal cancer following failure or intolerance to a first-line FOLFOX-based regimen. Strengths of this study included its double-blinded nature, placebo-controlled study design, multi-center participation, and large sample size. Investigators demonstrated an overall survival benefit of 1.6 months favoring ramucirumab with a manageable toxicity profile. In the Canadian setting, however, where first-line therapy for metastatic colorectal cancer continues to be predominantly FOLFIRI-based, the study findings of RAISE may not have a direct or immediate impact on our current treatment algorithms.
- CARE Oncology Faculty