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This year's American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) featured many highlights on gastroesophageal, gastric, and gastroesophageal junction (GE junction; GEJ) cancers. In this video, Samuel Klempner, MD, of Massachusetts General Hospital in Boston, discusses several of the key abstracts in this area and their implications for clinical practice.

Following is a transcript of his remarks:

In the non-metastatic setting, we saw survival rates for the Neo-AEGIS trial. A brief reminder, this was a trial comparing versus perioperative chemotherapy -- largely -- in this trial in GE junction adenocarcinomas primarily. And really with 3-year survival rates, there was absolutely no difference between CROSS versus MAGIC.

Of course, one of the main criticisms is that this trial was largely using an outdated chemotherapy. Only about 15% of patients got FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel). But nevertheless it was exactly identical outcomes at 3-year survival rates.

When we move into the first-line metastatic setting, I think this is where the biggest splash of perhaps all of ASCO GI was, in that we have a new target and a new drug. So Claudin 18.2, which has been on everybody's radar for a while, we saw the first presentation of the phase III first-line SPOTLIGHT trials. This was built on the phase II FAST trial, suggesting a survival benefit to the addition of Claudin-targeting antibodies in Claudin-positive tumors.

But a brief reminder, that SPOTLIGHT was a randomized phase III trial comparing FOLFOX, or standard chemotherapy, with or without zolbetuximab, which is an anti-Claudin 18.2 antibody. All patients were Claudin 18.2 positive. This is selected on an immunohistochemistry assay with a cutoff of 75% of cells showing positive staining.

And really what we saw is that with a primary endpoint of progression-free survival, the trial extended progression-free survival. So it hit the primary endpoint and it also extended overall survival. In fact, I believe this is the longest overall survival we've seen to date in a first-line gastroesophageal trial, with a survival in the experimental arm of about 18 months.

So I think everyone expects that this will ultimately lead to a global approval of this agent. We also saw some press release data suggesting that the GLOW trial, which was a complementary phase III trial looking at the same question but using CAPOX [capecitabine and oxaliplatin] as the chemotherapy backbone, was also positive. So now we have a totality of two phase III trials asking the same question in slightly different populations that are both positive.

So it's expected that this agent will become a new tool for us, and then it will be up to the field to decide how best to integrate this into clinical practice. Certainly there's a lot of interest in combining this with immune therapy. So you could envision a triplet of chemotherapy with zolbetuximab with immunotherapy in Claudin-positive patients.

There was some other nice data at ASCO GI in the gastroesophageal space. We saw , which was a phase III trial similar to CheckMate 649 in that it was asking the question of adding PD-1 immunotherapy on top of chemotherapy. This was a randomized phase III trial looking at tislelizumab in combination largely with 5-FU and oxaliplatin. And again, they showed improvement in overall survival in the PD-L1 positive patients, in this case a score greater than 5% in their phase III. We haven't seen it in all the randomized patients yet, but fully expect that that will likely be positive.

And finally in the late-line setting -- so this is a setting where patients had two or more prior lines of therapy -- we saw the . So this was a phase III randomized controlled trial of regorafenib [Stivarga], which is a multikinase, primarily anti-angiogenic, agent, against placebo. And so this is a positive phase III -- the magnitude of benefit is there, but the absolute increase in overall survival, which was the primary endpoint, remained somewhat limited.

And I think it's important to note it's a positive phase III trial without a biomarker selection. It's also relevant to note that many of these patients had prior VEGF-directed therapy in the form of ramucirumab [Cyramza]. However it does highlight that this is a difficult patient population to treat, and unfortunately the outcomes do remain poor. But this may become another tool for us.

So, overall for upper GI and gastric esophageal, this was a really great ASCO GI meeting.

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