Cyramza® (ramucirumab): Användning vid Hepatocellulär cancer

Phase 3 Studies

REACH-2

A global, randomized, double-blind, placebo-controlled study compared ramucirumab plus BSC and placebo plus BSC in patients with advanced HCC and elevated baseline AFP following first-line sorafenib.¹

Patients were eligible for participation if they had

• diagnosis of HCC (histological or radiological imaging confirmation) or in the absence of histological confirmation a diagnosis of cirrhosis and HCC with classical imaging characteristics 

• BCLC stage C or stage B refractory or not amenable to locoregional therapy

• Child-Pugh Class A

• ECOG PS score of 0 or 1

• baseline AFP ≥400 ng/mL

• prior sorafenib treatment (discontinued due to progression or intolerance), and

• adequate hematologic and biochemical parameters.¹

Patients were randomly assigned in a 2:1 ratio (stratified by geographic region, baseline ECOG PS, and macrovascular invasion) to receive ramucirumab 8 mg/kg plus BSC (n=197) or placebo plus BSC (n=95) every 14 days until disease progression or unacceptable toxicity, or until discontinuation criteria were met.¹ 

The primary endpoint was OS. A significant improvement in OS was observed among patients who received ramucirumab plus BSC compared with patients who received placebo plus BSC (8.5 vs 7.3 months; HR=0.710 (95% CI: 0.531-0.949); p=.0199).¹

Any grade TEAEs that occurred while on treatment and due to any cause in ≥20% of patients who received ramucirumab plus BSC were

• fatigue

• peripheral edema

• hypertension

• decreased appetite

• liver injury/failure

• bleeding/hemorrhagic events

• abdominal pain, and

• proteinuria.¹

More detailed information on the REACH-2 study is available upon request. 

REACH

A multicenter, randomized, double-blind, placebo-controlled trial was conducted in patients with advanced HCC following first-line treatment with sorafenib.²

Patients were eligible for participation if they had

• diagnosis of HCC (histological or radiological imaging confirmation)

• BCLC stage C or stage B refractory or not amenable to locoregional therapy

• Child-Pugh Class A

• ECOG PS score 0 or 1

• prior sorafenib treatment (discontinued due to progression or intolerance)

• adequate hematological, and

• biochemical parameters.²

Patients were randomly assigned in a 1:1 ratio (stratified by geographic region and etiology of liver disease) to receive ramucirumab (8 mg/kg IV every 2 weeks) plus BSC (n=283) or placebo (every 2 weeks) plus BSC (n=282) until disease progression, unacceptable toxicity, withdrawal of consent, or death.²

Overall survival was the primary endpoint. The median OS was 9.2 months in the ramucirumab arm compared to 7.6 months in the placebo arm (HR=0.87; 95% CI: 0.72 - 1.05; p=.14).²

Grade ≥3 adverse events occurring in ≥5% of patients in either treatment arm were

• hypertension

• malignant neoplasm progression

• ascites

• asthenia

• increased aspartate aminotransferase

• thrombocytopenia

• increased blood bilirubin, and

• hyperbilirubinemia.²

More detailed information on the REACH study is available upon request.

Phase 2 Study

A first-line, single-arm study was conducted to assess the use of ramucirumab in patients with advanced HCC.³

Patients were eligible for participation if they had

• Child-Pugh A or B liver disease

• CLIP score 0 to 3, and

• ECOG PS of 0 or 1.³

Patients (n=42) received treatment with ramucirumab 8 mg/kg IV every 2 weeks until disease progression or unacceptable toxicity.³

The primary endpoint of PFS was 4.0 months (95% CI: 2.6-5.7).³

The most common grade ≥3 TEAEs that occurred included

• hypertension

• gastrointestinal hemorrhage

• infusion-related reactions, and

• fatigue.³

References

1. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296. http://dx.doi.org/10.1016/S1470-2045(18)30937-9

2. Zhu AX, Park JO, Ryoo B-Y et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2015;16(7):859-870. http://dx.doi.org/10.1016/S1470-2045(15)00050-9

3. Zhu AX, Finn RS, Mulcahy M, et al. A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular cancer. Clin Cancer Res. 2013;19(23):6614-6623. http://dx.doi.org/10.1158/1078-0432.CCR-13-1442.

Glossary

AFP = alpha-fetoprotein

BCLC = Barcelona Clinic Liver Cancer

BSC = best supportive care

CLIP = Cancer of the Liver Italian Programme

ECOG = Eastern Cooperative Oncology Group

HCC = hepatocellular carcinoma

HR = hazard ratio

IV = intravenous

OS = overall survival

PFS = progression-free survival

PS = performance status

TEAE = treatment-emergent adverse event