Second-line ramucirumab beneficial to select liver cancer patients
Use of ramucirumab in the second-line treatment of hepatocellular carcinoma (HCC) after prior sorafenib yields survival gains with a manageable safety profile in Japanese patients with elevated alpha-fetoprotein (AFP) levels, according to a subgroup analysis of the phase III REACH-2 trial.
“The clinical benefits of ramucirumab observed in the Japanese subpopulation were in line with those observed for the overall REACH-2 study population,” the investigators said.
In the global REACH-2 population of advanced HCC patients with AFP ≥400 ng/mL (n=292) who had progressed on or could not tolerate sorafenib, treatment with second-line ramucirumab prolonged overall survival (OS) by about 30 percent compared with placebo (hazard ratio [HR], 0.710, 95 percent confidence interval [CI] 0.531–0.949; p=0.0199). [Lancet Oncol 2019;20:282-296]
The current subgroup analysis included 59 Japanese patients, 41 (median age, 71 years) of whom were in the active treatment arm and 18 (median age, 68 years) in the placebo arm. Those who received ramucirumab were more likely to be male, have higher Child–Pugh score A-5, longer disease duration, and have higher median baseline AFP level.
The study drug produced a significant improvement in progression-free survival (PFS; HR, 0.282, 95 percent CI, 0.144–0.553) and a numerical increase in OS (HR, 0.599, 95 percent CI, 0.303–1.187). The objective response (7.3 percent vs 0 percent) and disease control rates (70.7 percent vs 33.3 percent) were also higher than with placebo. [J Gastroenterol 2020;55:627-639]
Grade ≥3 treatment-emergent adverse events (TEAEs) occurred more frequently in the ramucirumab arm than in the placebo arm, with the most common being hypertension (15 percent vs 11 percent). Additionally, the proportion of patients who developed adverse events of special interest (AESIs), including liver injury/liver failure (low-grade ascites) and bleeding/haemorrhage events (lepistaxis), among others, was higher in the active treatment arm.
“This is the first report of an agent showing clinical benefit as second-line treatment in a population of Japanese patients with HCC following prior sorafenib,” according to the investigators, adding that the survival improvements seen with ramucirumab were consistent with those observed in the subpopulation of Japanese patients with similar characteristics in the REACH study (PFS: HR, 0.261, 95 percent CI, 0.391–0.986; OS: HR, 0.464, 95 percent CI, 0.232–0.926). [J Gastroenterol 2017;52:494-503]
Pooled patient-level efficacy data of the REACH-2 and REACH revealed that the survival gains obtained with ramucirumab were greater in the Japanese subpopulation than in the overall population (median OS, 10.8 vs 8.1 months). [Ann Oncol 2018;29(suppl 5):LBA-001]
“As discussed previously in relation to the REACH study, the reasons for numerically longer survival of ramucirumab-treated Japanese patients compared with the overall study population(s) require further elucidation, but may include differences in Japanese patient characteristics or disease management that result in greater benefit from an effective therapy,” the investigators pointed out.
“Conventional chemotherapy is of limited or no benefit in patients with advanced HCC. For a long time, sorafenib, a multikinase inhibitor, was the only systemic treatment shown to improve OS in patients with HCC. However, [the drug] is associated with significant toxicity, with approximately 30 percent of patients stopping treatment because of intolerance,” they noted. [Lancet 2018;391:1301-1314; N Engl J Med 2008;359:378-390; Cancer Sci 2008;99:159-165]
Taken together, the current data provide evidence that ramucirumab is an active and well-tolerated second-line treatment option for Japanese patients with HCC and elevated AFP levels, they added.