touchONCOLOGY spoke with editorial board member Michael K Gibson (Vanderbilt University, Nashville, TN, USA) to discuss his highlights from the American Society of Clinical Oncology (ASCO) Annual Meeting, 2–6, June 2023 in the field of upper GI oncology, including the phase 3 ATTRACTION-5 study and a randomized, phase II study assessing toripalimab for the treatment of treatment of locally advanced resectable gastric or gastroesophageal junction adenocarcinoma.
Disclosures: Michael K Gibson has no financial or non-financial conflicts of interest to declare in relation to this video.
Support: Interview and filming supported by Touch Medical Media. Interview conducted by Sophie Nickelson.
Filmed as a highlight of ASCO 2023
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Transcript
My name is Michael Gibson. I am a medical oncologist, and I practice at Vanderbilt University, which is in Nashville, Tennessee, in the States. My focus is on esophageal gastric cancers, and I run that clinical program here at Vanderbilt, and I also am a translational researcher in that field.
Today, I’d like to talk about two abstracts presented at the oral abstract session for upper GI cancer at the ASCO 2023 meeting in Chicago earlier this month. Both abstracts involve esophageal gastric cancer. They actually have a couple of things in common which will be a theme. Number one, they both involve gastroesophageal junction and gastric adenocarcinoma. Number two, they are both looking to improve upon the outcome obtained with surgery alone. And number three, they’re looking at the addition of immunotherapy to chemotherapy in the perioperative setting.
The first abstract is ATTRACTION-5, it comes out of Asia, and the goal of this study was to assess whether adding immunotherapy to adjuvant chemotherapy for resected gastroesophageal adenocarcinoma improved outcome. The primary outcome was recurrence-free survival. They had randomized approximately 800 patients who had a D2 margin-negative resection and the control arm, adjuvant therapy, was either XELOX or, excuse me, they call it CapeOX, same difference, or S-1. Patients were enrolled agnostic of PD-L1 expression, and they all had adenocarcinoma. The primary outcome of RFS was not achieved in this study. So adding nivolumab to chemo was no better than chemo alone. For some perspective, if I may, CheckMate 577 looked at a similar approach. This was published in the last two years or so. It was run by Ronan Kelly. In that case, the patients had either adeno or squamous cell cancer of the esophagus or GE junction and not gastric. The patients included adeno and squame histologies and they all got neoadjuvant chemoradiotherapy. So in 577, the experimental intervention was to add nivolumab to patients who did not have a pathologic complete response to neoadjuvant chemoradiotherapy, and the control arm was observation. So a number of differences, but it’s curious because, to me at least, because CheckMate 577 was positive for overall survival benefit. So something to contemplate.
The second of the two studies is looking at another immune checkpoint inhibitor called toripalimab. Coherus provides this drug for study. This also looked at gastric and GE junction adenocarcinoma only. All the patients were to have, eventually, surgery as part of a perioperative approach. The patients were deemed worth studying in the frontline setting because of data from JUPITER-06, which looked at the addition of tori, as I’ll call it, to taxol carbo in the frontline recurrent metastatic setting. And in that case, adding immunotherapy improved the clinical outcome. So then they move this type of approach to the frontline setting for patients with resectable adenocarcinoma of the stomach and GE junction. The perioperative therapy was SOX or XELOX, in this case and the experimental intervention was to add toripalimab to this chemo regimen in the frontline setting. The primary outcome was not so much a survival benefit outcome, it was actually a surgical outcome. So they only got through the preoperative portion of the study, but the overall approach is perioperative kind of like the FLOT-AIO study, but they hadn’t gotten that far. And it was a phase 2 design with only 108 patients. So the idea is that the endpoint of path response could be assessed to determine whether it was worth expanding the trial to a larger phase 3 intervention. Their control path response rate based on, at least from what I can tell, the FLOP trial was 20 percentish. This is something called TRG 0 or 1. This is defined in the abstract. But it’s essentially how much tumour is, I guess, killed by the preoperative therapy. Their alternative hypothesis was that adding the toripalumab to the chemo would increase this path response rate to 40%. And in fact, they met their primary endpoint. The response rate in the chemo only arm was 20%, but in the chemo-tori arm it was 44%. So they concluded that they met their phase 2 endpoint, and I presume the plan is to move this into a larger study to look at the survival benefit when you give not only preoperative chemo immuno, but also postoperative.
So two pretty neat studies. Lot of other good stuff, of course, but I wanted to highlight these two. I think that the theme again just to finish up is trying to improve the standard of care of multimodality care for resectable stomach and GE junction adenocarcinoma by adding immunotherapy in some way, shape, order, or sequence. One of the studies was not positive and the other had a nice early increase in path response rate endpoint.
