- In the REACH-2 trial of patients with sorafenib-treated hepatocellular carcinoma (HCC) and baseline α-fetoprotein (AFP) concentrations ≥400 ng/mL, second-line ramucirumab yielded superior OS and progression-free survival (PFS) vs placebo.
Why this matters
- AFP has been suggested as a risk biomarker, but has not gained broad acceptance.
- REACH-2 is the first positive phase 3 trial performed in a biomarker-selected HCC patient population.
- 292 patients with sorafenib-treated HCC and AFP ≥400 ng/mL were randomly assigned 2:1 to treatment with placebo or 8 mg/kg intravenous ramucirumab every 2 weeks.
- Funding: Eli Lilly.
- At follow-up (median, 7.6 months), ramucirumab resulted in extended OS (median, 8.5 months vs placebo, 7.3 months; HR, 0.710; P=.0199) and PFS (2.8 months vs 1.6 months; HR, 0.452; P<.0001>
- No significant difference observed with respect to objective response, median time to deterioration in FHSI-8 total scores, or ECOG performance status.
- Grade ≥3 treatment-emergent adverse events (AEs) with ramucirumab vs placebo included hypertension (13% vs 5%), hyponatremia (6% vs 0%), and increased aspartate aminotransferase (3% vs 5%).
- Serious AEs of any grade and cause: 35% with ramucirumab vs 29% placebo.
- Treatment-emergent AEs led to 3 deaths in the ramucirumab group.
- Severe cirrhosis excluded.