Do you recognize this patient?
This is a patient with rapidly progressing mCRC*. Someone whose disease progressed within 6 months on first-line treatment with bevacizumab + mFOLFOX6.
Someone who is aware of their situation, but is not surrendering to it.
- Diagnosed with tumor in distal colon and multiple liver metastases
- ECOG PS 1
- KRAS exon 2 mutation positive
- Developed additional metastases in liver and right lung
Can you picture one of your patients?. Someone who, in the face of adversity, remains determined? Someone who is ready for what’s next?
For your patients whose mCRC has progressed
CYRAMZA: Mechanism of Action
What would you do at disease progression in mCRC?1
CYRAMZA + FOLFIRI demonstrated a statistically significant improvement in OS1 with consistent results in patients regardless of time to disease progression or KRAS status1-3
RAISE 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 pre-specified and exploratory.
- 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
- 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§
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
- 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.
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
SELECT IMPORTANT SAFETY INFORMATION
- An increased incidence of severe hypertension occurred in patients receiving CYRAMZA. Across five clinical studies in 1916 patients with various cancers treated with CYRAMZA, the incidence of all Grade hypertension occurred between 11-26%. Grade 3-5 hypertension incidence ranged from 6-15%.
- Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every two weeks or more frequently as indicated during treatment. Withhold CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA for medically significant hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.
The labeling for CYRAMZA contains warnings and precautions for hemorrhage and GI hemorrhage, including severe and sometimes fatal events; gastrointestinal (GI) perforations, a potentially fatal event; impaired wound healing; arterial thromboembolic events (ATEs), including serious and sometimes fatal events; hypertension; infusion-related reactions; worsening of pre-existing hepatic impairment, reversible posterior leukoencephalopathy syndrome (RPLS); proteinuria including nephrotic syndrome; thyroid dysfunction; and embryo-fetal toxicity. CYRAMZA should be permanently discontinued in patients who experience severe bleeding, a GI perforation, an ATE, uncontrolled hypertension, severe IRR, RPLS, or urine protein >3 grams/24 h or nephrotic syndrome. CYRAMZA should be discontinued in patients who develop wound healing complications that require medical intervention.
In RAISE, the most common adverse reactions (all Grades) observed in CYRAMZA with FOLFIRI-treated patients at a rate of ≥30% and ≥2% higher than placebo with FOLFIRI were diarrhea (60% vs 51%), neutropenia (59% vs 46%), decreased appetite (37% vs 27%), epistaxis (33% vs 15%), and stomatitis (31% vs 21%). The most common serious adverse reactions with CYRAMZA with FOLFIRI were diarrhea (3.6%), intestinal obstruction (3.0%), and febrile neutropenia (2.8%); 20% of patients treated with CYRAMZA with FOLFIRI received granulocyte colony-stimulating factors.