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Expert Discusses New Targets, Developments on the Horizon in Gastric Cancer

Shannon Connelly
Published Online:4:02 PM, Tue September 27, 2016

Howard S. Hochster, MD

As gastric cancers continue to be classified into different subtypes, oncologists will now have the opportunity to improve treatment by determining which targeted agents are appropriate for which subtypes, said Howard S. Hochster, MD.
Also on the horizon in the gastric cancer field, Hochster said, is the exciting possibility of using immunotherapy, specifically anti-PD1 or PD-L1 agent combinations, for the treatment of certain subsets of patients in the gastric cancer space.
In an interview with Targeted Oncology, Hochster, professor of Medical Oncology, and Yale Cancer Center Associate Director (for Clinical Sciences), discusses new targeted therapies currently being investigated in the field of gastric cancer, the importance of the proper classification of subtypes, and the challenges that still remain in regard to treatment of the disease.

TARGETED ONCOLOGY: Are there any new targets currently being investigated in gastric cancer?

Hochster: I think we are all fairly excited about the possibility of using immunotherapy, specifically anti–PD-1 or PD-L1 agents with or without anti–CTLA-4, and perhaps other immunomodulators in combination with these checkpoint inhibitors. These will eventually be directed toward specific subsets of patients in the gastric cancer universe.

TARGETED ONCOLOGY: Why is it important for gastric cancers to be properly classified?

Hochster: That is the way we will make the most progress in treating the disease, by understand the biology better. For example, if we tried using trastuzumab in all gastric cancer patients, rather than selecting out the ones that were HER2-positive, we wouldn’t see efficacy. Similarly, for some of the biologics that we didn’t test in select, population the studies were negative. Given the more susceptible population, we may have a much more robust effect of the therapeutic agent.

TARGETED ONCOLOGY: What are the most recent developments in terms of treatment in gastric cancer? What do you see on the horizon?

Hochster: I think the use of ramucirumab and other anti-angiogenics will lead to more developments in that area. There are options for neoadjuvant therapy with some of these drugs. The immune checkpoint inhibitors are going to be very important, especially if we understand the patients who are most likely to benefit from them.
There are other HER2 agents that are coming along as well that would be useful for trastuzumab failures. I think there are a number of important targeted agents that are coming along now, focused on the appropriate patient populations.

TARGETED ONCOLOGY: What challenges still remain with regard to treatment?

Hochster: Our therapy is only partially effective, so I think every dimension of treating gastric cancer could be improved. There could be better tactics, better biologics, and a better understanding of the molecular subsets. These are all areas that are challenges to me, and they all present opportunities to improve treatment in gastric cancer.

TARGETED ONCOLOGY: What other questions remain in the field of gastric cancer?

There is a major need for understanding the clinical implications of a The Cancer Genome Atlas (TCGA) classification. We know they identify certain kinds of biological clustering, but we don’t know the clinical and therapeutic implications of those subsets yet.  Therefore, we don’t know how to use those to prognosticate or direct therapy.  There is a lot of work to be done in those spheres.

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