Practice-Changing Regorafenib Data at 2018 ASCO GI Cancers Symposium

John L. Marshall, MD


January 31, 2018

Editorial Collaboration

Medscape &

Hello, everybody, this is John Marshall from Medscape and Georgetown University. I'm home after the big American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2018. Even though I have some interesting data to share with you, I wish ASCO would stop presenting all of the abstracts at the big meeting in Chicago and instead push everybody to present their abstracts at their specialty meetings. Then we would have really good abstracts, time to think about them, and time to talk to each other. We could bring to the big meeting the top 10 or top 20, or only the plenary-session kinds of abstracts. We would benefit across all of the disease groups from that kind of a strategy. They will never do it. Let's pound on them, and maybe, just maybe...

It was a great meeting. We enjoy going there together. We spend most of the time talking with each other and not seeing new science, but there is some important new science to tell you.

You all know PEGPH, pegylated recombinant human hyaluronidase, with the ability to target stroma, particularly in pancreas cancer. We were excited to see what we hoped would be a positive study of FOLFIRINOX plus the PEGPH agent. The surprise was that it was negative. In fact, it was not only a tie, but worse if you received the experimental arm.[1] It was another disappointment in pancreas cancer.

There was a lot of talk about whether we should now close the gemcitabine/nab-paclitaxel with PEGPH trial. I think the answer to that is no. There are differences between fluorouracil (5-FU)-based therapy and gemcitabine-based therapies, so I would encourage us to continue on and hopefully complete that study to see if in fact we will have some benefit.

Turning our attention to colorectal cancer, several important, practice-changing papers were presented. Tanios Bekaii-Saab, our good friend down at Mayo in Arizona, presented the ReDOS trial.[2] Regorafenib was randomized to start at 160 mg daily versus 80 mg daily and then ramped up or down depending on toxicity. Lo and behold, we would have accepted a tie in that trial and would have been happy with that. In fact, the low-dose regimen, starting at 80 mg and going up, did better in terms of overall survival than the reverse. These are really fairly interesting and exciting data. For most of our patients, I think this justifies starting regorafenib at 80 mg, seeing them weekly, and then increasing the dose according to their toxicity and tolerance. There might be a survival advantage in doing that.

The second really interesting regorafenib study[3] was done by a Japanese group only in patients with KRAS codon 12 mutations, though there may be some other patients that might be in the mix here. This was a sequencing question: If you have a wild-type RAS-mutant patient, which should you give first—regorafenib or cetuximab? They randomized patients between the two sequences. Much to my surprise, the regorafenib-first arm did better. It suggested that giving regorafenib first, before any epidermal growth factor receptor (EGFR) therapy, might, in fact, improve outcomes. Even though this was a small randomized trial, it may influence practice patterns and practice guidelines as we go forward. These were two interesting papers around regorafenib, suggesting an easier dosing strategy with improved outcome, and using it earlier in the sequence may be better, in fact.

There were more data around sidedness. Right-sided stage II and stage III patients had a worse disease-free survival. This came out of 3- versus 6-month data.[4] Interestingly, 6 months did not solve that. Just because you have a right-sided colon cancer does not mean that you should get 6 months of adjuvant chemotherapy based on the big IDEA conglomeration, if you will.

Our good friend, Dr Bendell, updated us on the cobimetinib and atezolizumab study[5] in microsatellite-stable colon cancers. As more patients have been accrued, the response rate has fallen. We are less excited than we were when we first heard about these data, but there are a lot more data to come in that space. Keep watching. We are hoping that we can convert some microsatellite-stable patients with colon cancer into immunoactive tumors.

It was a good meeting. There were some interesting and practice-changing data. Please, ASCO, push all of the abstracts out to the disease-specific meetings. Then we promise we will bring the best of our stuff to Chicago. This is John Marshall from Medscape.


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