New GI Cancer Studies: Curious Failures, Hidden Gems

This is John Marshall, director of the Otto J. Ruesch Center for the Cure of Gastrointestinal (GI) Cancers at Georgetown University in Washington, DC.

One of the projects we work on is to provide a fairly regular review of the literature out there for GI tract cancers and pick some of the top papers that have just been published. This isn't so much dealing with abstracts, which we cover extensively around the time of the major oncology meetings, but rather published, final data. With that in mind, I picked some studies that I thought would be interesting for us to review.

More Data From NORDIC-VII

The first is a fascinating publication of data from the NORDIC-VII study. This already-published study^[1] looked at chemotherapy using a regimen of bolus 5-fluorouracil (5-FU)/folinic acid and oxaliplatin, plus or minus cetuximab, in the frontline setting for metastatic colorectal cancer (mCRC). Although this study was negative, researchers provided an updated analysis using RAS and BRAF enrichment, the results of which were just published in British Journal of Cancer.^[2]

What was really surprising to me is that this is still a negative study. We have no idea why this is true. This is the right molecular profile, and the only real variable that differs from other trials is simply the use of a regimen of bolus 5-FU with oxaliplatin. Although we do not really understand what this is about, the take-away lesson is that maybe bolus—which I still see being done often—is not the best way to give 5-FU today, particularly in combination with other biologics.

Effectiveness of FOLFOXIRI/BEV

The second publication is another chemotherapy-based trial, which was published in JAMA Oncology in July.^[3] Researchers provided a pooled analysis of 11 studies using the combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI/BEV) in frontline regimens in mCRC. They looked at a bunch of studies done using that multiple-drug, frontline combination. Specifically, they looked at the rate of resection, response rate, and other outcomes. They reported an objective response rate of 69% response rate, a very high surgical conversion rate of 28.1%, and an overall survival around 30 months. And, of course, this is not with any molecular enrichment.

We keep pushing away FOLFOXIRI/BEV as a frontline treatment choice because we say that it is too spicy and all that, even though we are using it in pancreatic cancer quite a bit. Therefore, I think we need to take this analysis seriously, particularly in patients who do not have molecular profiling data available, who have bulky tumors, and in whom you need a response. This is a study that offers a very interesting way to go for those patients, for conversion therapy. I think that maybe, based on this analysis, we are underutilizing FOLFOXIRI/BEV in the frontline setting.

Recommending Aspirin After a Diagnosis of Colorectal Cancer

The third paper was published in the European Journal of Cancer^[4] and is one of my favorites because it looks at the use of aspirin in patients diagnosed with colorectal cancer and compares it with other antiplatelet drugs. In point of fact, it showed that aspirin was good and the other antiplatelet drugs did not add anything, which I think is really important. Post–colorectal cancer aspirin use was associated with a significant increased overall survival and hazard ratio of 0.41. That is a dramatic positive hazard ratio; the other antiplatelet drugs did not have that benefit.

If your patient can tolerate aspirin after a diagnosis of colorectal cancer, it is almost a must that they should be on it. I know most of us are making that recommendation, but this is one more paper saying we should do it.

Trastuzumab Emtansine for HER2-Positive Gastric Cancer

The last topic actually encompasses two studies, GATSBY^[5] and TH3RESA,^[6] which deal with HER2-positive gastric cancer and are really complicated. These papers were published in Lancet Oncology and look at the second- and third-line use of the fancier trastuzumab with the toxin attached to it, trastuzumab emtansine, which is already approved in breast cancer.

Interestingly, the second-line GATSBY clinical trial was in fact negative, but the third-line TH3RESA clinical trial did show benefit with this targeted therapy.

I do not know what to make of that. One argument is that unlike in breast cancer, maybe we should not do HER2 through-lines of therapy. Instead, maybe a break is in order somewhere there, like we do in some of the other targeted agents. Or maybe different drugs will come in here and have a different impact.

It's still very important to look at HER2 expression in your gastric cancer patients. Then, I think we will see more activity in second- and third-line, looking at new approaches for bringing in HER2 targeting in those downstream lines of therapy.

In conclusion, these are the publications that I think will influence you, perhaps change your practice, and some that you just need to keep your nose out for. But all are important and worthy of noting. Hopefully we will have another batch of papers to talk about in a month.

This is John Marshall, here at the Ruesch Center at Georgetown. Thank you.

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