AFP-High (AFP ≥400 ng/mL) advanced HCC
Clinical trial efficacy: REACH‑2
CYRAMZA, as a single agent, is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha-fetoprotein (AFP) of ≥400 ng/mL and have been treated with sorafenib.
SELECT IMPORTANT SAFETY INFORMATION
- CYRAMZA can increase the risk of gastrointestinal perforation, a potentially fatal event. Across five clinical studies in 1916 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.
CYRAMZA® (ramucirumab) significantly reduced the risk of death1
REACH‑2 OS: Median—Months (95% CI)1
- The percentage of deaths at the time of analysis was 75% (147 patients) and 78% (74 patients) in the CYRAMZA and placebo treatment arms, respectively1
CYRAMZA OS analysis based on prespecified patient subgroups3
- This was a prespecified exploratory analysis of the major outcome measure. The analysis was not adjusted for multiplicity or powered to detect the effect of CYRAMZA between subgroups. Therefore, no conclusions of statistical or clinical significance can be drawn.3
CYRAMZA significantly reduced the risk of disease progression or death1
REACH‑2 PFS: Median—Months (95% CI)1,4
- The percentage of events at the time of analysis was 87% (172 patients) and 91% (86 patients) in the CYRAMZA and placebo treatment arms, respectively1
- 26 of 172 events in CYRAMZA-treated patients and 9 of 86 events in placebo-treated patients were deaths1
REACH‑2 ORR: Percentage of Patients (95% CI)
REACH‑2 Trial Design
The phase III REACH‑2 trial evaluated the efficacy and safety of CYRAMZA vs placebo in patients with advanced HCC after prior sorafenib therapy and high baseline serum AFP levels ≥400 ng/mL.1 Major efficacy outcome measure was OS. Supportive efficacy outcome measures included PFS and ORR. All patients were ECOG PS 0 or 1, with BCLC stage B (and no longer amenable to locoregional therapy) or C disease, and Child-Pugh A liver disease. Patients were stratified by geographic region, macrovascular invasion, and ECOG PS. Patients were randomized 2:1 to CYRAMZA 8 mg/kg + BSC (n=197) or placebo + BSC (n=95) every 2 weeks (on days 1 and 15) of each 28-day cycle.1,5,6
SELECT IMPORTANT SAFETY INFORMATION
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 (IRR), including severe and sometimes fatal events; 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.
The most common adverse reactions (all Grades) observed in single agent CYRAMZA-treated HCC patients at a rate of ≥15% and ≥2% higher than placebo were fatigue (36% vs 20%), peripheral edema (25% vs 14%), hypertension (25% vs 13%), abdominal pain (25% vs 16%), decreased appetite (23% vs 20%), proteinuria (20% vs 4%), nausea (19% vs 12%), ascites (18% vs 7%). The most common serious adverse reactions with CYRAMZA were ascites (3%) and pneumonia (3%).