FDA Approves Single-Agent Ramucirumab for HCC Treatment

The Food and Drug Administration (FDA) approved ramucirumab (Cyramza) as a single-agent treatment for patients with hepatocellular carcinoma (HCC) with an alpha fetoprotein (AFP) of ≥ 400 ng/mL and have been previously treated with sorafenib (Nexavar), according to the FDA.

The approval was based on the multinational, randomized, double-blind, placebo-controlled REACH-2 trial, where 292 patients were randomized 2:1 to receive either 8 mg/kg of ramucirumab plus best supportive care (197 patients) or placebo plus best supportive care (97 patients) every 2 weeks as an intravenous infusion until disease progression or unacceptable toxicity. Eligibility criteria for the REACH-2 trial included a diagnosis of HCC and Barcelona Clinic Liver Cancer (BCLC) stage B or C, Child-Pugh score of A, AFP ≥400 ng/mL, disease progression with first-line sorafenib, and disease refractory to or not amenable to local treatment.

Patients on the trial received a median of 6 doses (range 1-51) of ramucirumab. Median duration of exposure was 12 weeks (range 2-107). About a quarter of patients (24%; n=197) received the drug for 6 months or longer.

The estimated median overall survival (OS)—the study’s primary endpoint—was 8.5 months for patients in the ramucirumab arm compared with 7.3 months for patients in the placebo arm (HR 0.71; 95% CI: 0.53, 0.95; p= 0.020). The median follow-up time was 7.9 versus 6.6 months in the experimental and control arms, respectively. The objective response rate showed a numerical advantage for the ramucirumab group (4.6% vs 1.1%; nonsignificant at P = .1697 ). Comparison of disease control rates showed a significant advantage for the ramucirumab arm (59.9% vs 38.9%; P = .0006).

Common adverse events (AE) for ramucirumab were fatigue, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, and ascites. Common laboratory abnormalities were hypoalbuminemia, hyponatremia, and thrombocytopenia. AE-related treatment discontinuations occurred in 18% of ramucirumab-treated patients.

According to the drug’s prescribing information, there are certain AEs that should lead to the permanent discontinuation of ramucirumab, including grade 3 or 4 hemorrhage, all grade gastrointestinal perforation, all-grade arterial thromboembolic events, uncontrollable hypertension, grade 3 or 4 infusion-related reactions, and proteinuria with urine protein levels that are greater than 3g per 24 hours or in the setting of nephrotic syndrome.

It is recommended that ramucirumab is administered intravenously at 8 mg/kg every 2 weeks.