CRC Builds Up STEAM in Midst of Blizzard

John L. Marshall, MD


February 08, 2016

Editorial Collaboration

Medscape &

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This is John Marshall for Medscape, back from the Gastrointestinal Cancers Symposium (GICS, or GI ASCO). Actually, I chickened out. I was there; it was Thursday, and "Snowmageddon" or "Snowpocalypse" was happening on the East Coast. In no uncertain terms, my wife said, "You are coming home to shovel." So, I cancelled everything that I was supposed to do, got on a plane, and flew home. In the end, it was probably a good decision, because the rest of the gang is just trickling in. I bless them for staying and sticking it out.

I'm here to summarize what happened at the meeting, and where we are in gastrointestinal (GI) cancer. Let's go on a high level first.

There is big confusion out there in terms of what we should do today for GI cancers, particularly colorectal cancer. You should be testing all of your patients for extended RAS, not just KRAS, and you should be testing all of your patients for microsatellite instability (MSI).[1,2] Both of those have significant clinical implications. All of your colorectal cancer patients—not just stage II or III or IV—should have RAS and MSI testing going forward.

There are three new medicines for GI cancers. The two in the colorectal space you know about. Regorafenib (Stivarga®) has been out there for a while, and we are still trying to figure out its optimal dose and schedule. [3,4] The more we look, the more we see that this is a good drug; we just need to figure out how to use it.

The newcomer on the block, TAS-102 (trifluridine/tipiracil [Lonsurf®]),[5,6] is basically a novel fluoropyrimidine with tipiracil, an inhibitor of metabolism [of trifluridine, which helps to maintain trifluridine blood levels]. It's a well-tolerated oral drug but can cause myelosuppression. It has dose and schedule issues as well.

Both of these drugs are in the third-line refractory space. Both have important survival advantages, so don't leave them on the table. We need to play those cards for our patients in metastatic disease.

A new drug in the pancreas space is liposomal irinotecan (Onivyde™), a novel agent. I've given it now to one patient. Is it different from irinotecan? We are going to find out. But certainly, there are positive data in the second-line and refractory settings in combination with fluorouracil/leucovorin infusion.[7] It may affect how we treat folks with metastatic pancreatic cancer, possibly having Onivyde come forward [as an earlier-line therapy].

There was a lot of very good science presented at GI ASCO. In terms of stuff that has an immediate impact on clinical care, not a lot is going on in gastric cancer. The biggest stuff is immune therapy in the MSI-high tumors, whether they be colon or other. That is why you have to check for those incredibly important positive data. It's still a small subset of patients, but an important subset to identify and treat with new checkpoint inhibitor-type approaches.[8]

In colorectal cancer, the biggest study presented that may have an influence on you is known as STEAM [Sequential Triplet and Avastin Maintenance].[9] Johanna Bendell, a good friend and great researcher, led and presented this clinical trial. It had three arms: concurrent FOLFOXIRI-BEV, sequential FOLFOXIRI-BEV (alternating FOLFOX and FOLFIRI, given in two cycles, two cycles, and two cycles), or FOLFOX-BEV. The punch line of this clinical trial was that FOLFOXIRI-BEV did perform a little better—the alternating arm not so much. There was a slightly higher primary surgical resection rate of metastatic disease with the FOLFOXIRI-BEV.

Used with permission from Johanna Bendell, MD, Nashville, Tennessee

That is just one more piece of evidence that throwing everything at patients in frontline may in fact have some outcome advantage. But it is not a definitive study. I left, so I did not hear Johanna's take or the spin on it at the meeting. My take is that there are clearly certain times in metastatic colon cancer where frontline FOLFOXIRI-BEV is a reasonable regimen to employ, and this study gives more evidence to support that.

I was sad about leaving the meeting early; I enjoyed the snow, it was great. We kept our power, which is always good. But GI ASCO is just a fabulous meeting—to see friends, to catch up, and to talk science. We can't do this at the big ASCO; it's just too big, and we are all running too much. But in San Francisco each year, we stop, have meals together, and think. We have time to really plan how we are going to reach out and do a better job in terms of clinical translational research and, one day I hope, cure GI cancers.

I dug out. I'm at the office. Snowmageddon just finished here in Washington, DC. But I missed most of GI ASCO. John Marshall for Medscape.


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