Clinical trial efficacy: RAISE
Metastatic Colorectal Cancer
CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
RAISE trial: Efficacy
CYRAMZA + FOLFIRI demonstrated a statistically significant improvement in OS1
RAISE ITT OS: Median—Months (95% CI)1
OS: The percentage of deaths at the time of analysis was 69% (372 patients) and 74% (397 patients) in the CYRAMZA + FOLFIRI and placebo + FOLFIRI arms, respectively1
- Treatment effect was consistent across prespecified stratification factors
Supportive outcome measure: Median PFS was 5.7 months with CYRAMZA + FOLFIRI1 (95% CI: 5.5, 6.2) (n=536) vs 4.5 months with placebo + FOLFIRI (95% CI: 4.2, 5.4) (n=536) (HR=0.79 [95% CI: 0.70, 0.90]); P<0.001
- PFS: The percentage of events at the time of analysis was 89% (476 patients) and 92% (494 patients) in the CYRAMZA + FOLFIRI and placebo + FOLFIRI arms, respectively1
- 73 of 476 events in CYRAMZA-treated patients and 64 of 494 events in placebo-treated patients were deaths.
SELECT IMPORTANT SAFETY INFORMATION
- CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. In 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade and Grade 3- 5 gastrointestinal perforations ranged from <1-2%.
- Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation
Consistent results in patients regardless of time to disease progression or KRAS status1-3
RAISE Subgroup OS: Median—Months (95% CI)
The RAISE trial was not adequately powered, nor error-controlled, for subgroup analyses. Treatment differences observed in these subgroups cannot be regarded as statistically significant. The analyses described here were prespecified and exploratory.
- Patients with time to disease progression on 1L ≥6 months (HR=0.86 [95% CI: 0.73, 1.01]): Median OS: 14.3 months with CYRAMZA + FOLFIRI (13.1, 15.5), n=411, vs 12.5 months with placebo + FOLFIRI (11.7, 13.6), n=407†
- Patients with wild-type KRAS (HR=0.82 [95% CI: 0.67, 1.00]): Median OS: 14.4 months with CYRAMZA + FOLFIRI (12.7, 16.1), n=267, vs 11.9 months with placebo + FOLFIRI (10.8, 13.3), n=275‡
‡ For KRAS mutant patients, the percentage of deaths at the time of analysis in the CYRAMZA + FOLFIRI arm was 72.9% (196 patients) and 75.9% (198 patients) in the placebo + FOLFIRI arm. For KRAS wild-type patients, the percentage of deaths at the time of analysis in the CYRAMZA + FOLFIRI arm was 65.9% (176 patients) and 72.4% (199 patients) in the placebo + FOLFIRI arm.3
RAISE Trial Design (N=1072)
The phase III RAISE trial evaluated the efficacy and safety of CYRAMZA plus FOLFIRI vs placebo plus FOLFIRI in patients with mCRC with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Major efficacy outcome measure was OS. Supportive efficacy outcome measure was PFS. All patients were required to have ECOG PS 0 or 1. Patients were stratified by geographic region, KRAS mutation status, and time to disease progression after the beginning of first-line treatment (<6 months vs ≥6 months). Patients were randomized 1:1 to receive either CYRAMZA 8 mg/kg (n=536) or placebo (n=536), in combination with FOLFIRI every 14 days.1