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
Impaired Wound Healing
- CYRAMZA has the potential to adversely affect wound healing. CYRAMZA has not been studied in patients with serious or non-healing wounds.
- Withhold CYRAMZA for 28 days prior to elective surgery. Do not administer CYRAMZA for at least 2 weeks following a major surgical procedure and until adequate wound healing. The safety of resumption of CYRAMZA after resolution of wound healing complications has not been established.
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
REACH-2 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
REACH Trial Outcomes
Median OS, the major efficacy outcome measure for the ITT population in the REACH trial, did not meet statistical significance.9
9.2 months with CYRAMZA + BSC (n=283; 95% CI: 8.1, 10.6) vs 7.6 months with placebo + BSC (n=282; 95% CI: 6.0, 9.3); HR=0.87 (95% CI: 0.72, 1.05)9
- The percentage of deaths at the time of analysis was 77.0% (218 patients) and 79.4% (224 patients) in the CYRAMZA and placebo treatment arms, respectively12
The analyses for the AFP subgroups (≥400 ng/mL and <400 ng/mL) were prespecified and exploratory without controlling for type 1 error. Observations made from these analyses cannot be considered statistically significant.
Median OS in the prespecified subgroup of patients with AFP ≥400 ng/mL showed an improvement in OS9: 7.8 months with CYRAMZA + BSC (n=119; 95% CI: 5.8, 9.3) vs 4.2 months with placebo + BSC (n=131; 95% CI: 3.7, 4.8); HR=0.67 (95% CI: 0.51, 0.90)9
- The percentage of deaths at the time of analysis was 83.2% (99 patients) and 88.5 % (116 patients) in the CYRAMZA and placebo treatment arms, respectively12
Median OS in the prespecified subgroup of patients with AFP <400 ng/mL showed no improvement in OS9: 10.1 months with CYRAMZA + BSC (n=160; 95% CI: 8.7, 12.3) vs placebo + BSC (n=150; 95% CI: 9.9, 13.1); HR=1.09 (95% CI: 0.84, 1.43)9
- The percentage of deaths at the time of analysis was 72.5% (116 patients) and 72% (108 patients) in the CYRAMZA and placebo treatment arms, respectively12
More than 500 AFP-High patients were studied in the REACH Program, adding to the body of evidence in these difficult-to-treat patients.1,5,9
The REACH Program pooled analysis was prespecified and exploratory without controlling for type 1 error. Observations made from this analysis cannot be considered statistically significant.
OS in the pooled analysis of AFP-High patients was consistent with results from REACH-2
REACH Program Pooled OS: Median-Months (95% CI)10
REACH-2 Major Outcome Measure: Median OS with CYRAMZA (n=197) was 8.5 months (95% CI: 7.0, 10.6) vs 7.3 months (95% CI: 5.4, 9.1) with placebo (n=95) (HR=0.71 [95% CI: 0.53, 0.95];P=0.0201
CYRAMZA significantly reduced the risk of disease progression or death1
REACH-2 PFS: Median Months
- 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)
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; posterior reversible encephalopathy syndrome (PRES), including fatal events; 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, PRES, or urine protein >3 grams/24 h or nephrotic syndrome.
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%).
REACH Trial Design
The phase III REACH trial evaluated the efficacy and safety of CYRAMZA vs placebo in patients with advanced HCC after prior sorafenib therapy. Major efficacy outcome measure was OS. Supportive efficacy outcome measures included PFS and ORR. The ITT population of patients was 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 and etiology of liver disease. Patient subgroup analysis was prespecified by baseline serum level of AFP ≥400 ng/mL. Patients were randomized 1:1 to CYRAMZA 8 mg/kg + BSC (n=283) or placebo + BSC (n=282) every 2 weeks (on days 1 and 15) of each 28-day cycle until disease progression, unacceptable toxicity, or death.9
The Major Outcome Measure for the ITT population within the REACH trial did not meet statistical significance.9
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
For your patients with AFP ≥400 ng/mL: CYRAMZA1
The first and only biomarker-driven therapy approved for AFP-High patients with advanced HCC1,5,7
National Comprehensive Cancer Network® (NCCN®)
Ramucirumab
Specifically for patients with advanced HCC*
and AFP ≥400 ng/mL with disease progression
with a Category 1 recommendation as a subsequent treatment option in the
NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines®]8†
CATEGORY 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.8
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.