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Emerging Developments in NETs, Liver Cancer

Chelsea LoCascio
Published: Tuesday, Nov 21, 2017

We couple that with the ability to shrink tumors, with things like PRRT and better surgical and liver-directed techniques, you can take a patient who is feeling pretty sick or has a carcinoid tumor or NET that dominates their entire life, and render them to a point where it’s not at the constant forefront of their mind. As we see more and more options to help with that, symptom control is one of the more unmet needs. We need more [focus there], but it’s been encouraging to see it be able to change people’s lives. 

What ongoing trials do you find to be exciting?

The question of immunotherapy is going to be interesting. There are quite a few immunotherapy studies that are looking at NETs. They have enrolled very quickly. We expect more to be done in this field; whether or not you can generate an immune response to neuroendocrine cancer cells is going to be interesting. That, I would argue, is one of the hotter topics that’s out there.

The other types of therapies that are going to be moving forward will continue to target the somatostatin receptors, much like somatostatin analogs and PRRT that have been used before, but targeted more aggressively and specifically, and be able to offer sequential lines of therapy. Targeted therapies, such as everolimus (Afinitor) or cabozantinib (Cabometyx), are certainly not done. They continue to show activity. One of the big questions that’s out there is, “Is cabozantinib going to meet its endpoint and offer an additional line of therapy for these patients?” We don’t know yet. That trial is currently ongoing.

You gave another lecture on liver cancer. What is important to highlight here?

What has been challenging for medical oncologists is that we haven’t really had drugs. Sorafenib (Nexavar) made an explosion onto the scene, and it did so because it was the first drug to show a significant benefit in these patients. It continues to demonstrate that benefit in a number of subsequent studies, so we are seeing it happen again and again. We need more than that for medical oncologists to get engaged with the field.

With the approval of regorafenib (Stivarga) in the second-line setting and the expedited approval of immunotherapy with nivolumab (Opdivo), we are starting to see other types of drugs work their way in so that medical oncologists have options for patients with advanced HCC.

What about lenvatinib (Lenvima)? Where are we with that agent in liver cancer?

Lenvatinib was in an interesting study. The issue of looking at lenvatinib with sorafenib is that those were compared to head to head. While there was a little bit of a trend of improvement in response rates with lenvatinib, the toxicity was noticeably higher. I wonder where that’s going to sit in the landscape. It offers an additional therapeutic option for patients with HCC. In people who a have a lot of familiarity with the drug, you may see it used in the frontline setting or other settings if it comes into the United States. However, people are a little bit more familiar with sorafenib.

I can’t say that the data shape and move the standard of frontline therapy, so I don’t know how much it is going to be used. There may be patients where you look at that response rate and say, “If we try to push a little bit more shrinkage, maybe this is a compelling option,” but you have to do so carefully. The lack of familiarity with it versus sorafenib, which has been around longer, will be interesting to see whether is uptake of it in the community. It certainly did demonstrate at least some degree of noninferiority in the frontline study.

What do you do for patients who relapse on regorafenib or sorafenib?

With most of those patients, we try to get them on clinical trials. You’re going to see that activity in immunotherapy be used to try to leverage an additional number of trials, including checkpoint inhibitors [and in combination] moving into the frontline and second-line settings, as well as additional immune-activating agents being sequentially added into the secondary lines. The immunotherapy signal is compelling.

It’s compelling not just because nearly every disease is showing at least about a 20% response rate with checkpoint inhibitors in some degree—which isn’t massive. It’s compelling in HCC because not much has traditionally shrunk these tumors and [also] been tolerable. While chemotherapy has had activity, it’s tended to hurt the liver as much as it helped and it has not translated to people living longer.

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