Immunotherapy, Emerging Agents Offer Hope in GI Cancers

Gina Columbus @ginacolumbusonc
Published: Thursday, Mar 16, 2017

Johanna C. Bendell, MD

Johanna C. Bendell, MD

Much ground is being covered in the space of gastrointestinal (GI) cancer treatment, with a focus on how more subsets of patients can benefit from immunotherapy agents alone or in combination and have improved, long-term outcomes.

“In terms of the evolution of the field of GI oncology, we are seeing small starts—small hope coming through across multiple tumor types,” said Johanna Bendell, MD, director of GI Oncology Research at Sarah Cannon Research Institute. “I don’t think we have hit the big one yet, but we are on the cusp of seeing some real improvements in how patients are doing, particularly with immunotherapy combinations and modifying immunotherapies, so it works for more patients with GI cancers.” 

PD-1 inhibitors in combination with CTLA-4 inhibitors is one example of a research method being studied in these malignancies, while more novel approaches include the incorporation of stemness inhibitors, like napabucasin (BBI-608) to target cancer stem cells, Bendell adds.

In an interview during the 2017 OncLive® State of the Science Summit on GI Cancers, which Bendell chaired, she provided further insight on the emerging treatment landscape in GI malignancies, with a special focus on cancers of the liver, GI tract, and pancreas.

OncLive: What are the latest developments in the liver cancer?

Bendell: We have known that drugs that block the angiogenesis pathway for liver cancers, such as sorafenib (Nexavar), do work for patients with liver cancer. But now, we’ve seen data that show that another VEGF inhibitor, regorafenib (Stivarga), works for these patients, as well.

What is even more exciting is that we’re seeing data that immunotherapies are very promising agents for the treatment of patients liver cancer.  

Can you elaborate on the significance of the immunotherapy data?

In liver cancer, they have looked at checkpoint inhibitors like anti­–PD-1/PD-L1 agents alone and in combination with CTLA-4 inhibitors. Different drug companies have looked at their different agents and they’re all currently in clinical trials, but are looking very promising. They are also looking particularly promising is patients with hepatitis, particularly hepatitis C. 

Regorafenib currently has a priority review designation with the FDA for liver cancer. What did we see in the pivotal study that could lead to its approval?

We saw recent data at the 2017 GI Cancers Symposium from the RESORCE study, which took patients with liver cancer who progressed on sorafenib and randomized them to regorafenib or placebo. What we saw was an improvement in both progression-free survival (PFS) and overall survival (OS) using regorafenib versus placebo. 

What major questions remain with regorafenib?

The biggest thing with regorafenib is how to dose it safely and how to limit the toxicities that we see. Right now, the starting dose is 160 mg per day. If you are going to start that high, you definitely need to educate patients about the toxicities, and have them call in if they start to have any of them so you can hold the drug quickly before it becomes too bad. 

Some practitioners, though, are starting at lower doses—120 mg or even 80 mg. Currently in the colon cancer field, researchers are beginning a trial that will compare starting at the higher dose versus lower dose of regorafenib to see if it’s just as effective to start at a lower dose rather than the higher.

You also spoke on gastric cancer at tonight’s meeting. What is new in this area?

It is such an amazing time in the development of drugs for patients with gastric cancer. We’ve seen that immunotherapies—checkpoint inhibitors alone and even in combination—help patients with gastric cancer.

We saw our first randomized phase III study’s data at the 2017 GI Cancers Symposium, which looked at patients with gastric cancer that was refractory to at least 1 line of therapy. These patients were treated with the PD-1 inhibitor nivolumab (Opdivo) versus best supportive care. We did see an improvement in OS in these patients, finally giving us phase III evidence that immunotherapy is active for patients with gastric cancer. 

What role could immunotherapy have in gastric cancer treatment?

We see that immunotherapy is very active in patients with gastric cancer; about 20% to 30% of them have a chance of responding to immunotherapy. Now, we also have to think about what’s going to happen to the other 70% to 80% of patients who don’t respond.

One way people are looking at it is combining immunotherapy—like PD-1/PD-L1 inhibitors with CTLA-4—as well as newer immunotherapy targets that are in development. 

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