ASCO GI 2023: SUNLIGHT Study

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EP: 1.ASCO GI 2023: SUNLIGHT Study

EP: 2.Examining the Role of ctDNA

EP: 3.Real-World Evidence (RWE) Supporting Use of ctDNA

EP: 4.Utilizing RWE to Address Unmet Needs for CRC

EP: 5.ASCO GI 2023: SPOTLIGHT Study

EP: 6.Opportunities for Innovation in GI Cancer Treatment Landscape

John L. Marshall, MD: We have a lot of miles to go in colorectal cancer [CRC]. We have so many unmet needs. First, we really don’t understand what makes cancer tick. We are only just getting to the point where we’re separating it molecularly. And believe it or not, it matters where the primary is, right-sided vs left-sided. We’re only just beginning to understand the role of the microbiome in how cancers respond. But if you look at molecular targets, the No. 1 thing we need to figure out is RAS—how to target all of those RAS mutations that more than half of our patients have with metastatic colorectal cancer [mCRC]. But we are making progress. [However,] there’s still miles to go.

One of the most important abstracts that was presented is actually teaching old dogs new tricks. So we all know about TAS-102. This is Lonsurf; trifluridine and tipiracil. It’s been approved as a single agent in CRC and some other cancers as well. And we’ve been using it, but we’ve been sort of, I would say, unenthusiastic about using it because it didn’t really cause much in the way of response and stable disease in only some patients. We had some phase 2 data combining it with bevacizumab [Avastin], which actually showed some very interesting positive results. And the SUNLIGHT study is the phase 3 version of that phase 2 trial. So it’s a 2:1 randomization, where half the patients received TAS-102; trifluridine and tipiracil by itself. The other group had bevacizumab added. 246 patients were treated on this. And what was dramatic about this was that there was a 3-month improvement in overall survival. And in fact, there were response rates seen now when we don’t see response rates with either drug by themselves. But put it together, we saw some patients with tumor regression and a hazard ratio of 0.61. Look we’ve been doing studies in frontline where we’ve accepted therapies with less of a hazard ratio or higher hazard ratio than that. So this was really a positive study and I think immediately transforms the standard for third-line treatment for patients with mCRC. So you know we’ve got sort of ox [oxaliplatin]-based chemotherapy frontline, usually iri [irinotecan]-based second line. Although some people reverse that, some people combine them all together. But you have ox [oxaliplatin] and iri [irinotecan] as your main chemotherapies, you have biologics, we use a lot of bev [bevacizumab] in the United States. The rest of the world, not so much. But a lot of bev [bevacizumab] in the frontline and often in the second line, particularly in RAS mutated patients. We have EGFR-targeted agents in those 15% of patients who are candidates for EGFR therapy. And then you have third-line therapy, and it was always between regorafenib [Stivarga] and TAS-102. I think this study firmly establishes this combination. In many ways, I’m sort of joking, this is a validation of how good bevacizumab is in CRC. So many of these patients, in fact, most of these patients had had prior bevacizumab. And despite that, we saw this delta of 3 months and a hazard ratio of 0.61 and responses. So there was an immediate change in the standard of care and an immediate impact on our patients. Many of us, frankly, were doing this already. And it was nice to be validated with this phase 3 study that what we had done as early adopters was in fact the right thing. So [this was an] important positive survival benefit study in refractory colon cancer using 2 drugs you’re already familiar with.

If you think about what this is adding, so Lonsurf [TAS-102], by itself, pushed the survival by a couple of months. TAS-102 plus bev [bevacizumab] pushes it by an additional chunk of time. Also, you get responses. So it further extends the benefit that we were seeing with the 1 drug alone.

I think most guidelines will have this updated as soon as they go to the next printing, quite honestly. You’ve got phase 3 positive data. And of course, the company is going for an official label for this. So a label change is in the works. But I think it’s already kind of an asterisk in the guidelines now. I think that asterisk will come off.Where I think it’s going to go ultimately is shifting more to the earlier and earlier lines of therapy, this kind of approach is sort of what I like to think of as second maintenance therapy for our patients of an oral plus a simple IV regimen with good control, good progression-free survival, and some additional responses.

We cannot forget that this is not curative therapy. Clinical trials are an option for patients all the time. This study was in patients who went onto a clinical trial using the standard of care drugs. So every patient should want clinical trials. When people refer to clinical trials, they often think of them as a sort of last-ditch effort. And there are therapies out there looking for patients who really have run out of other options. But research should be embedded in everything we do. Certainly, patients who have had this combination would still have regorafenib as an approved additional option. And clinical trials, as I said, are good at any time.

Transcript edited for clarity.