Key Takeaways in the Treatment of HCC - Episode 5

Key Takeaway 5: High AFP is a Biomarker for Ramucirumab


Richard Finn, MD: Alpha-fetoprotein [AFP] has been a biomarker in liver cancer for some time. Its exact role has been somewhat difficult to define. It’s not a very good screening test in and of itself, because only about two-thirds of liver cancers make AFP. If you’re using it as a screening test, you’ll miss one-third of patients, which is why screening should be imaging-based, like an ultrasound, and then if you want to add AFP to that, that’s acceptable. We know that patients with a high AFP have a worse prognosis than those who don’t have a high AFP. In the context of making treatment decisions, we now have data that suggest that patients with a high AFP benefit from ramucirumab in the second-line setting.

The data come from the REACH-2 study. This was a follow-up to the first study of ramucirumab, which took all patients. You may remember that ramucirumab is a monoclonal antibody to the VEGF [vascular endothelial growth factor] receptor. In the first REACH study for patients who progressed on sorafenib, ramucirumab did not improve survival significantly over placebo. Retrospectively, it was identified that patients who had a high AFP did get a benefit, and that led to the REACH-2 study. The REACH-2 study looked at ramucirumab versus placebo for patients who had an AFP greater than 400 ng/mL. Patients progressed on sorafenib, and if they had an AFP greater than 400 ng/mL and were in Child Pugh stage A, they were candidates for the study. This study read out last year, and it was a positive study.

This study showed that ramucirumab improved survival. The absolute delta between the median survival of the placebo arm and the treatment arm was around a month-and-a-half. The hazard ratio and risk reduction for death were significant. It was around 0.78, and that was more than a 20% decrease in the risk of death with the addition of ramucirumab to best supportive care.

Again, what’s interesting about ramucirumab is that it doesn’t have a high response rate for single-agent responses. It does tend to slow progression, and there’s a very distinct tail to the curve; there are a number of patients who have long-term survival. Even though that’s not captured so well with the median, if we look at the PFS [progression-free survival] curves or the TTP [time to progression] curves, we see that we’re doubling PFS and TTP. That’s translating into the survival benefit.

As a monoclonal antibody, which is different from the kinase inhibitors, it’s very well-tolerated. Its toxicity is very much attached to its target, which is the VEGF receptor. We need to watch for hypertension, proteinuria, and some fluid retention. For patients who have been on kinase inhibitors and are having hand-foot syndrome or diarrhea, I think ramucirumab is a very good option to give them a break from some of those adverse effects, especially if they have a high AFP.

Transcript Edited for Clarity