Second-Line Therapy: Monoclonal Antibody

Transcript:

Masatoshi Kudo, MD, PhD: Ramucirumab is a very good agent because it’s a monoclonal antibody. Adverse events are very few, and the tolerability is very good. Relative dose intensity is 98% globally and also in Japan. Japan has a large elderly population. The average age of HCC [hepatocellular carcinoma] patients is more than 70 years old, 75 or so. Even in Japanese patients, that tolerability of ramucirumab is 98%, similar to global patients.

We prefer a dosing of greater than 400 mg, and we prefer to use the ramucirumab, even after lenvatinib or sorafenib. In sequential therapy, the first-line agent is very strong. Sometimes there are more adverse events with sorafenib than the sorafenib and lenvatinib. But ramucirumab has very few adverse events, and quality of life is very good.

Regarding sequential therapy, there was another subanalysis clearly showing that ramucirumab does not impair liver function. We prefer to use ramucirumab as a second-line agent, then patients can tolerate very well for a while and can rest. Then if the peak progress of disease appears, we change to the third-line agent. So we prefer ramucirumab.

Kate Kelley, MD: The role for ramucirumab after first-line bevacizumab-containing regimen is not clear, noting that both of them target the VEGF pathway, with ramucirumab as a VEGF receptor 2–targeted monoclonal antibody and bevacizumab as a VEGF-targeted monoclonal antibody. There is precedent for using the 2 drugs both in a disease such as colorectal cancer, but we don’t know the efficacy of the sequence in hepatocellular carcinoma. My inclination in the second-line setting after atezolizumab plus bevacizumab would be a multikinase inhibitor, such as cabozantinib, bearing in mind that it was established in the CELESTIAL trial after a more permissive first- or second-line population, including third-line patients after a variety of first- and/or second-line regimens. But ramucirumab certainly will continue to play a role in patients with high alpha-fetoprotein, particularly those who have exhausted other options.

Minsig Choi, MD: The REACH-2 study has shown that ramucirumab is an effective agent in patients with refractory HCC. For many of these TKIs [tyrosine kinase inhibitors], the major reason this works is by blocking the VEGF receptor pathway, and we know that ramucirumab is a monoclonal antibody that blocks VEGF receptor 2 pathways. Antigenesis is important in liver cancer and is basically the mechanism how it’s spread. One advantage of ramucirumab is that it’s given as a parenteral, so the patient doesn’t have to take any pills either every day or twice a day. Another thing is that the toxicity for ramucirumab is a lot easier compared with some of the TKIs. We think the oral agents are more beneficial and have fewer adverse effects. But some of these TKIs, which are multikinase blockade—like regorafenib and cabozantinib—have toxicities like hand-foot syndrome and fatigue.

My clinical experience has been that ramucirumab is a little easier to tolerate than some of the TKIs. But every patient is different, so you have to really look at how the patient did well in their first-line setting. Some people want to take oral agents. Some people like to come to the infusion center and see the nurses. They like the parenteral infusion and they don’t like swallowing their medications, or they have co-pay issues and the parenteral option is better.

With the coronavirus pandemic, a lot of patients don’t want to come to the hospital and the cancer centers, so perhaps the TKIs or oral agents might be better than the parenteral infusions.

Transcript Edited for Clarity