Immunotherapy in Liver Cancer

Insights From: Arndt Vogel, MD, Hannover Medical School; Oliver Waidmann, MD, Goethe-Universitat Frankfurt am Main


Arndt Vogel, MD:
Immunotherapy is great, at least we assume that it’s really great. But—and this is unfortunately a “but” that is getting bigger and bigger. Actually, we have seen very promising data with nivolumab. And I think patients who respond to immunotherapies have a really, extremely good prognosis. The problem is that not all patients with HCC really respond to immunotherapy. So, similar to other solid tumors, we only see response rate of around 20% to 25%. For these patients, immunotherapy is really a great treatment. It has only a few side effects. It’s very well tolerated by our patients, and these patients have long-term disease control. And as far as we can see so far, we do not really have a decline in liver function and there is no effect of any of the underlying liver diseases. So, this is really great and good news.

On the other hand, we have a lot of patients who rapidly respond and who do not derive any clinical benefit from treatment with immunotherapies. So, what we need are either biomarkers to identify those patients who respond to immunotherapies, or we need to find more or other innovative combination therapies where we combine local therapies or other systemic therapies with immunotherapies to increase the number of patients who really derive a benefit from immunotherapies.

Oliver Waidmann, MD: CheckMate-040 study investigated nivolumab in patients with hepatocellular carcinoma for systemic treatment. And this was a phase I/II trial setting, so it means that in the first part, they had a dose escalation study. They started with a lower dosage, and they found 3 mg/kg is the optimal dose. And there was also dose expansion cohort. About more than 200 patients were treated with nivolumab. The patients were quite heavily pretreated, so more than 70% of these patients had systemic treatment before and I think more than 60% had sorafenib. The study was just recently published and we found really impressive data in these patients. In the patients who had been pretreated and were infected with HBV or HCV infection, the median overall survival was more than 13 months. And, in the cohorts, a median overall survival was not even reached.

It’s always difficult to do cross-trial selections, but in the RESORCE trial, patients who received regorafenib as second-line treatment after sorafenib, the median overall survival was 10 months. And these were also really select patients, but only the patients who came along with sorafenib—and this is just a small proportion of patients—could get regorafenib. So, these were selected patients and these were, more or less, not selected patients. I think really there’s an importance of the efficacy, but we also had much less side effects compared to TKIs in these patients. I think there was 25% or something like this of 3/4 grade toxicity, but it was only, more or less, a laboratory finding. So, there was no diarrhea, no other severe diseases or complications, so they are really good data.

Transcript Edited for Clarity 

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