Pembrolizumab Boasts Benefit, Tolerability in Gastric Cancer

Brandon G. Smaglo, MD


February 03, 2015

Editorial Collaboration

Medscape &

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My name is Brandon Smaglo, from the Ruesch Center for the Cure of Gastrointestinal Cancers, part of the Lombardi Comprehensive Cancer Center at Georgetown in Washington, DC. We are about to have our second blizzard of the week here in DC, so it is hard to believe that just a week ago we were in a very different climate in sunny San Francisco, attending this year's Gastrointestinal Cancers Symposium. This is always a great event. It is an opportunity to hear some of the great work that has been done over the past year in the management of these very difficult-to-treat cancers.

Right now there is probably no more hot-button topic in the management of cancer or in the developing management of cancer than immunotherapy. It has great promise, and naturally we want to see where it is going to find its role in the management of GI cancers as well as other tumors where it has already shown some benefit.

New Balance of Safety, Efficacy in Gastric Cancer?

To that end, the first study I would like to review today deals with immunotherapy. A great study,[1,2] which was presented by Dr Levy from Stanford, looked at the management of gastric cancers specifically, using a PD-L1-targeted monoclonal antibody, pembrolizumab. For this study, patients were eligible if their tumors were expressers of PD-L1, and approximately 40% of the patients whose tumors they evaluated met that criterion. Not quite all of those patients went on to enter the study, for a variety of reasons. Dr Levy found that there was a reasonable benefit from this therapy. At 6 months, the overall survival for this patient population was about 69% (as they reported), which is very good, especially if you consider using immunotherapy, an agent that is perhaps better tolerated than cytotoxic chemotherapy will be. I can't comment on that because there hasn't been a head-to-head comparison yet, but it does cause us to wonder whether we haven't struck upon something that finds a new balance between safety/tolerability and clinical efficacy for our patients.

One thing that I think is important to note about this study, and what is still going to be controversial, is that the patients who were enrolled could have had a wide range of previous therapies, anything from no previous therapy to up to five different treatments. That raises a question that remains key as we try to understand and develop new drugs: Where are the immunotherapies going to fit into our treatment paradigm? What is the right role for these agents? Do we use them continuously? Do we use them and then stop and allow the immune system to continue to react against the tumors? Do we use them with chemotherapy, before chemotherapy, or after chemotherapy? Do we insert it between two different regimens? These are all going to be very important and critical questions as we go forward.

Certainly, as these data mature and are developed into later-phase trials, they will become key components. It was a great study. It was good to see that there is some role for these important agents in these cancers, where we have a continued need for better and more complete therapies. Kudos to these investigators for a nicely done study.

Can Chemo Be Omitted in Esophageal Palliative Therapy?

I want to shift gears and talk about our palliative management of the esophagus. A very nice multinational study[2] created some controversy on the floor. Looking at the palliative setting for esophageal cancer treatment by using either a combination of radiation with chemotherapy or radiation itself, the investigators found that there didn't seem to be a significant difference in terms of clinical efficacy or clinical benefit by omitting chemotherapy and using radiation as monotherapy. From a tolerance point of view, as one might expect, the radiation single-therapy arm was better tolerated in their report as compared with the concurrent therapies.

Of interest, an important deficiency that they acknowledged is that there was no chemotherapy-alone arm. Because this is an incurable disease and one in which we are worried about new metastases as well as local control, it is worth noting and inquiring about the benefit that might be seen in that group.

The other thing worth calling attention to is the impressive survival rates that were reported, impressive to the point that some may be a little skeptical of them. In the radiation-alone arm, patients had an average survival of 203 days, which is very good if you consider that these are patients who have a disease that was not in any way being systemically controlled.

This study does not answer any questions, nor is it paradigm-changing. But it does bring up a couple of considerations for palliative management: Do we need to be as aggressive with combined therapy? Is there a role for further exploration of a monotherapy? The answer to the exploration question is "yes." We need to better establish radiation as a therapy on the basis of this one study, but also take a look at how chemotherapy as a single modality of treatment might have performed as a separate arm in this study, to see where that would fit in the paradigm. Nevertheless, we are always looking for better palliative options for our patients, so this is something to consider.

It was a great meeting. If you weren't there, I hope that in the future you can make the trip. It is always very informative and educational. It is great to have some of the world leaders in gastrointestinal malignancies come together in one meeting. I found it very informative and very useful, and I hope that in the future you can, too.

I want to thank you very much for listening today. I'm Brandon Smaglo, coming to you from Georgetown in Washington, DC.


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