COMMENTARY

Practice-Changing GI Cancer Highlights From Virtual ASCO 2020

John L. Marshall, MD

Disclosures

June 12, 2020

This transcript has been edited for clarity.

This is John Marshall for Medscape. American Society of Clinical Oncology (ASCO) 2020 was the most efficient ASCO ever. I actually wore pants, you will be glad to know, as I watched all of the different talks, downloaded some, scrolled through some fast, and watched others a couple of times. My feet did not hurt. I didn't stay up too late and I didn't have to get up too early. Sure, I missed a lot, but I also got different things out of this format than I did before. On some level, I kind of liked this, but I'm going back to Chicago next year if we are allowed.

I wanted to emphasize all the cool stuff that happened in gastrointestinal (GI) cancers this year. There were a lot of important, practice-changing data. There is no way to cover all the information in one of these commentaries, so you will need to look out for an update or a review. But I wanted to touch on some big-picture themes that are really starting to hit home in GI cancer.

First, if you have not noticed this wave already, we are all about neoadjuvant chemotherapy now in GI cancers. In pancreas cancer, colon/colorectal cancer, gastric cancer, you are seeing this increasing trend of induction neoadjuvant systemic therapy. For pancreas, we are talking about FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin), but a study that looked at gemcitabine/Abraxane (nab-paclitaxel) basically said it played just as well in the neoadjuvant space for patients. We've got choices there. In the gastric space, we've got FLOT (docetaxel, oxaliplatin, leucovorin, and fluorouracil), but we're starting to add drugs to FLOT, such as HER2 targeting and the like. In colorectal, there was a nice study looking at FOLFIRINOX in rectal cancers that showed a very nice pathologic complete response (CR) rate and some progress there. It becomes a pretty nice model for us to test. Couple that with the IDEA study, which also showed some follow-up data of really no difference in overall survival in 3 vs 6 months (except maybe only a little bit in a small subset). If you give your few months of chemotherapy before surgery, then surgery becomes the last thing you do. (Although some studies cannot help but pile on more chemotherapy.) My feeling is that it's all going to be neoadjuvant treatment, then radiation in some cases, and then surgery, and then patients will be done with all their treatment and can go on with things. In some ways, this is going to be a quicker readout because we're going to have pathologic CR rates and tissue responses as part of our endpoints. I think trials can be smaller and faster, as we saw a lot of here at this ASCO. So, look out for neoadjuvant treatment in resectable GI cancers.

The second big area is new targets. Of course, BRAF is one of the big stories in colon cancer, thanks to Scott Kopetz and others who have participated in those studies. That overall survival data were published and I think we now have doublet therapy for BRAF V600E mutations. We are piling on HER2. We're seeing more and more new agents coming to the table with HER2. One of the cool, really new drugs is this T-DXd (trastuzumab deruxtecan), approved in breast cancer already but now getting tested in HER2+ gastric and colorectal cancers with some very nice response rates.

Last but not least is immunotherapy (IO) therapy. GI cancer research made the plenary session this year with a paper looking at frontline pembrolizumab versus chemotherapy—fascinating curves where the pembrolizumab actually did not perform as well initially compared to chemo. But the tail on that curve for pembrolizumab trumps by far whatever it could be done with the chemo arm. There will be crossover in the study, so it will mess with the overall survival. It really suggests in microsatellite instability (MSI)-high metastatic colon cancer that single-agent IO is certainly in play, with a lot of discussion that maybe we should be doing chemo plus IO as induction chemotherapy. Stay tuned for that. My guess is that we will have approval to do frontline IO in MSI-high colon cancer; whether this applies to the other GI cancers is yet to be determined. The biomarkers are not the same across all of that.

The story in liver cancer seems like "IO, IO, it's off to getting cured I go." They just keep doing better and better with frontline IO approaches in liver cancer. There is also a doublet in gallbladder cancer that looked very promising in frontline.

There are a lot of new treatments. IO is here to stay. Biomarkers are coming forward. New targets are being identified and therapies are being identified for those. Neoadjuvant therapy [is being used] for a shorter period of time. We'll get to go first as oncologists; the surgeons will get to go second.

I hope you have time to review some of what happened at ASCO across all of the different diseases. But for GI, this has been a very high-level summary of the big stuff that happened, in my opinion.

John Marshall, MD, is a leader in the research and development of drugs for colon cancer and other GI cancers, and has been the principal investigator of more than 150 clinical trials. Dr Marshall is the founding director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer, chief of the Division of Hematology-Oncology at Georgetown University, and the clinical director of oncology for Georgetown University Hospital.

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