Key data in gastrointestinal cancer: ESOPEC, TRANSMET, COLLISION, ARC-9

touchONCOLOGY coverage of data presented at ASCO 2024:

Practice-changing data in the field of gastrointestinal cancer was presented at ASCO 2024. To understand these, as well as the other highlights from the meeting, we spoke with Assistant Professor of Medicine (Medical Oncology), Yale School of Medicine, Dr Michael Cecchini.

In this interview, Dr Cecchini discusses the findings from the ESOPEC (NCT02509286), TRANSMET (NCT02597348), COLLISION (NCT03088150), ARC-9 (NCT04660812), ABBV-400 (NCT05029882) and other presentations, offering his valuable insights into the impact the results could have on clinical practice.

Associated abstracts:

Hoeppner J, et al. Prospective randomized multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (ESOPEC trial). ASCO Congress 2024, LBA1

Adam R, et al. Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET). ASCO Congress 2024, Abstract 3500

Meijerink MR, et al. Surgery versus thermal ablation for small-size colorectal liver metastases (COLLISION): An international, multicenter, phase III randomized controlled trial. ASCO Congress 2024, LBA3501

Weinberg  ZA, et al. ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC). ASCO Congress 2024, Abstract 3508

Sharma M, et al. First-in-human study of ABBV-400, a novel c-Met–targeting antibody-drug conjugate, in advanced solid tumors: Results in colorectal cancer. ASCO Congress 2024, Abstract 3515

Disclosures: Michael Cecchini has received grant/research support from National Cancer Institute, is on the advisory board for Incendia Therapeuetics and has received honoraria from Agenus, Loxo@Lilly, Arcus, Beigene, Bayer, Seattle Genetics, Taiho, Regeron, AstraZeneca, Daiichi Sankyo.

This content has been developed independently by Touch Medical Media for touchONCOLOGY and is not affiliated with ASCO. Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.

Click here for more content on gastrointestinal cancer & for further ASCO 2024 highlights visit here.

Transcript

Hello. I’m Michael Cecchini. I’m an assistant professor of medicine, at the Yale Cancer Center and the Yale University School of Medicine, and I’m here to talk about updates from the ASCO 2024 annual meeting.

I think one of the biggest studies that is important to review is the plenary session at a a trial in upper GI cancers, esophageal GE junction adenocarcinoma called the ESOPEC study. This study evaluated perioperative FLOT, so 5-FU/ leucovorin/oxaliplatin/docetaxel versus chemo and radiation with carboplatin/paclitaxel and radiation.

So worldwide, there’s been variations in in the the use of these regimens. In the US, largely, carboplatin, paclitaxel, or at least chemo and radiation has been the standard of care for esophagus and and largely a fair amount of gastroesophageal junction at no carcinomas.

And so this trial was trying to evaluate, is chemotherapy, perioperative chemotherapy, like we would use for gastric cancer, better than chemo radiation.

So one arm included radiation and chemo, and one arm was just chemotherapy. And then in this trial, we saw a very impressive improvement in median progression-free survival with perioperative FLOT, nearly double what we saw in the the chemo radiation arm, which is one of the reasons it, I think, was a plenary because this is practice changing information. We also saw a better 3-year disease-free survival, 3-year overall survival advantages with the perioperative chemotherapy without radiation. So not only were we seeing, improvements in survival, we were able to not give patients radiation, which may, result in fewer radiation-related toxicities long term.

At the end of the day, though, I think Dr Karyn Goodman, who did the discussant, did an excellent job reviewing the study and and future directions.

And at the end of the day, we’re still, not getting the outcomes we want for our patients. And I think future studies will probably see how radiation can build upon this better chemotherapy.

Chemotherapy is better than the chemo radiation, the chemo part of the chemoradiation that we do, in the control arm of that study. And so I think future studies will try and incorporate FLOT and radiation, to get better systemic control with the active chemotherapy and better local control with the chemo radiation. But for now, I think our practice will change that we’ll be using perioperative FLOP without without chemoradiation, so without radiation for our patients with esophageal and GE junction adenocarcinoma.

And for now, we’ll be treating our gastric tumors just like we treat our esophagus tumors, which is I think the first time that, we’ll be really doing that in the United States. Unanswered questions are how to incorporate adjuvant, immunotherapy, adjuvant nivolumab, which we used to do for these upper GI cancers when there’s residual disease after chemo RT. But I think starting this week in our clinics, we’ll be using perioperative FLOT for these patients.

There were also, some very interesting abstracts presented in the oral session for colorectal cancer. There was a TRANSMET study, which has been highly recognized for its novelty. This was evaluating patients with unresectable liver metastases and randomizing them to chemotherapy as would be the standard of care or liver transplantation.

This study was done in Europe. A highly selected patient population at centers with tremendous experience with this technique, and fewer than a hundred patients were ultimately enrolled in this study, 50% in the control arm, 50% in the investigational arm, just under 50 patients each. And we saw dramatic improvement in median overall survival with liver transplantation compared to standard of care chemotherapy, which demonstrates that there’s an overall survival benefit with the liver transplant approach for these patients that have unresectable liver metastases.

But the challenge is selecting these patients properly.

Despite these being extremely experienced centers with this technique, they still had their review committees reject over half the patients that were submitted for potential transplant. And we we’re not even seeing what the denominator there was for the patients that didn’t even make it to that kind of level of referral.

So highly selected group of patient population. And then the biggest issue, I think, is where are we going to get all the organs that are needed for those transplants because we have, a real scarcity there. But this is a very powerful study to show that we can really achieve excellent outcomes for our patients with this strategy that I think will lead to further development of research in this arena. Moreover, I think for highly specialized centers even in the US that can do this, it is proof of principle that there are patients that this should be done.

Other exciting studies, I think, was a COLLISION study and also in the colorectal cancer, oral abstract session that showed that ablating small liver lesions was equivalent to doing a surgical operation, on small liver lesions. So, I think that, gives us comfort that when there are small liver lesions that would be, difficult to resect, or other patient comorbidities that would maybe, make us on the fence about resection versus ablation. That ablation seems to be quite equivalent in those circumstances.

And then one other big surgical and medical oncology abstract was the metastatic setting for patients with colorectal cancer.

And patients, specifically, these are patients with multi- organ metastases, liver, lung, lymph node, multiple organ sites that had metastatic disease, whether or not we could do aggressive debulking surgeries and improve outcomes for those patients.

So these were not patients with limited isolated metastases, which is what we’ve historically done for surgery, but more aggressive surgeries with a higher possibility of leaving residual disease behind. So randomizing patients to that aggressive surgical debulking despite having widespread disease metastatic disease versus continuation of chemotherapy. And we really saw equivalence there. So that tells us that we should probably be a bit careful when recommending or performing surgery with patients that have widespread metastatic disease. It doesn’t necessarily change, our perception about patients that have isolated, especially all of the metastatic disease. So patients should still go to surgery as we do, and there’s a real possibility of of cure in those patients.

There were a few exciting, study drugs that were, presented for novel agents. There was the ARC-9 study presented by Dr Weinberg. And in full disclosure, I was a co-author on that presentation that looked at the novel adenosine receptor antagonist, etrumadenant, zimberelimab (anti-PD-1) plus FOLFOX/bevacizumab for third-line colorectal cancer versus regorafenib showed a very dramatic overall survival benefit of median overall survival of 19.7 months, the longest we’ve ever seen in a randomized trial in the third-line setting. I think that there’s, a lot to learn from this study.

There’s the question about the separation of components about the of of these drugs. But, frankly, with the dramatic overall survival benefit we’ve seen, I don’t think we can expect the FOLFOX to have been doing the heavy lifting, so to say, in this setting.

These are all patients that were refractory, had previously received FOLFOX. And based on the last, receipt of oxide platinum, whether or not it was a short term or long term re-exposure to that didn’t seem to make any difference. Moreover, most of the patients crossed over to that anyway.

I was also intrigued by the ABBV-400 data presented by Manish Sharma in the rapid oral abstract session, which showed, response rates above 20% in the late-line colorectal cancer population even in unselected patients with a novel adenosine antibody drug conjugate targeted CMAP with the topoisomerase 1 inhibitor payload.

So we’re starting to see the antibody drug conjugates. Maybe that will have a role in colorectal cancer. And I look forward to seeing further research in, in in those studies as well. It was a tremendous meeting.

We had excellent oral abstracts. We had a plenary this year in the other in the upper GI cancers.

And, I look forward to, exciting results in ASCO 2025.

Interviewer/Editor: Carla Junkier

Cite: Cecchini M. Key data in gastrointestinal cancer: ESOPEC, TRANSMET, COLLISION, ARC-9. touchONCOLOGY, July 23 2024.