Ramucirumab ups survival in advanced HCC regardless of prior TACE
The survival benefit with ramucirumab was consistent in patients with advanced hepatocellular carcinoma (HCC) and high alpha-fetoprotein (AFP) levels regardless of whether they were previously treated with transarterial chemoembolization (TACE), a post hoc analysis of pooled data from the REACH/REACH-2 studies shows.
Both REACH and REACH-2 were studies on the anti-VEGFR2 antibody ramucirumab in patients with advanced HCC who had progressed or were intolerant to sorafenib, with REACH-2 enrolling only patients who had elevated AFP (≥400 ng/mL) at baseline. Patients (Child-Pugh A, ECOG PS 0-1) were randomized 1:1 (in REACH) or 2:1 (in REACH-2) to receive intravenous ramucirumab 8 mg/kg or placebo once every 2 weeks.
Primary analysis from the REACH-2 study has shown that ramucirumab improved overall survival (OS) compared with placebo in HCC patients with elevated AFP. The current post hoc analysis aimed to find out if prior TACE treatment modify the survival benefit seen with ramucirumab, using pooled data of patients with high baseline AFP from both REACH and REACH-2 studies.
Overall, the efficacy of ramucirumab was similar between patients with and without prior TACE treatment (OS interaction, p=0.948), reported lead investigator Dr Tim Meyer of the Royal Free Hospital, University College London in London, UK at the ESMO 21st World Congress on Gastrointestinal Cancer. [ESMO GI 2019, abstract O-021]
In particular, OS was significantly longer with ramucirumab than placebo in patients who had prior TACE (median, 8.2 vs 5.2 months, hazard ratio [HR], 0.687, 95 percent confidence interval [CI], 0.530–0.890) and in those without prior TACE (median, 7.7 vs 5.0 months, HR, 0.705, 95 percent CI, 0.524–0.950).
Similarly, progression-free survival (PFS) was also longer with ramucirumab vs placebo regardless of whether patients had prior TACE treatment (median, 2.8 vs 1.5 months, HR, 0.557, 95 percent CI, 0.432–0.719) or no prior TACE (median, 2.8 vs 1.6 months, HR, 0.583, 95 percent CI, 0.431–0.787).
The results for both OS and PFS remained across analyses stratified by the total number of TACE treatments (0, 1, ≥1, ≥2), all in favour of ramucirumab (HRs, 0.656–0.766 for OS; HRs, 0.432–0.644 for PFS).
In general, the proportion of patients who had prior TACE treatment was similar in the ramucirumab and the placebo groups (56.6 percent vs 54.4 percent), with a median of one treatment in both groups. Among those who were previously treated with TACE, 65.6 percent had been treated once and 34.4 percent received two or more treatments.
According to Meyer, TACE treatment was more prevalent and frequently used in Asia compared with Western countries (75.2 percent in Japan and 69.8 percent elsewhere in Asia excluding Japan, compared with 38.5 percent in Western countries).
Summing up his presentation, Meyer said the data support the use of ramucirumab in advanced HCC patients with high baseline AFP regardless of prior TACE treatment.
The most common grade ≥3 treatment-emergent adverse event in the ramucirumab vs the placebo arms was hypertension, regardless of whether the patients had prior TACE (12.3 percent vs 3.3 percent) or no prior TACE (13.1 percent vs 4.0 percent).