ASCO 2022 | Advances in adjuvant and 1L immune checkpoint blockade for gastric and esophageal cancer
Ian Chau, MD, FRCP, The Royal Marsden NHS Foundation, London, UK, discusses the latest advances in the use of immune checkpoint inhibitors in gastric and esophageal cancers in the first-line (1L) and neoadjuvant setting. CheckMate 648 (NCT03143153) has established a new standard of care in patients with advanced esophageal squamous cell carcinoma where the addition of checkpoint inhibitors to chemotherapy demonstrated improved outcomes. Dr Chau also highlights the use of nivolumab in CheckMate 649 (NCT02872116) for adenocarcinoma, where patients with a CPS score of 5 or more reported improved survival. In the adjuvant setting, CheckMate 577 (NCT02743494) also highlighted improved disease-free survival with the use of immune checkpoint inhibitors, however, overall survival results have not been reported. Dr Chau also speaks on the DANTE study (NCT03421288), which was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, which is evaluating perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Transcript (edited for clarity)
In squamous cell cancer, esophagus, so CheckMate 648 study obviously established new set of care. But in fact, there are a number of other phase III randomized trials, which all reinforced the idea that by adding PD-1 antibody to chemotherapy, significantly improve overall survival compared to chemotherapy alone. So recently we have KEYNOTE-590, we also have a ASCO first study. We have another one called ORIENT-15 as well as Jupiter-06...
In squamous cell cancer, esophagus, so CheckMate 648 study obviously established new set of care. But in fact, there are a number of other phase III randomized trials, which all reinforced the idea that by adding PD-1 antibody to chemotherapy, significantly improve overall survival compared to chemotherapy alone. So recently we have KEYNOTE-590, we also have a ASCO first study. We have another one called ORIENT-15 as well as Jupiter-06. So all of these studies all show very consistent, significant survival benefit if you add PD-1 antibody to chemotherapy. But of course in CheckMate 648, there is an additional option of chemotherapy free ipilimumab plus nivolumab. So that’s really for squamous cell cancer.
For adenocarcinoma of the esophagus, esophagogastric junction and stomach. I think the main advance which is really from the CheckMate 649, with the addition of nivolumab to chemotherapy is significantly improved overall survival, compared to chemotherapy alone.
But here the main benefit is only seen in patients where the tumor PD-L1 CPS score is five or more. But I think this is now really changing the practice and the guideline across the world. In the adjuvant setting that probably mainly come from the 577 study. Now that is for tumor of the esophagus and esophagogastric junction, but they included both squamous cell and adenocarcinoma in that study. And patients in that study will undergo preoperative neoadjuvant chemoradiation followed by surgery. And you will randomize between nivolumab or placebo. And nivolumab significantly improved disease-free survival compared to placebo. And again, this is now licensed in many, many countries around the world and is incorporated in the new guideline.
But what we are very eagerly waiting from that study is the overall survival results, which is not yet reported. Because we really like to see the overall survival benefit as well. But that’s really using the strategy of preoperative chemo radiation. Another strategy is looking at what we call comparative chemotherapy are you given chemotherapy before and after surgery for gastric adenocarcinoma or junctional adenocarcinoma. And instead of care is currently given palliative [inaudible 00:02:49].
They are now both randomized control trial has finished recruitment as well as those which are ongoing. So the KEYNOTE-585, actually randomized patients between perioperative plus chemotherapy plus or minus pembrolizumab, although that’s about 800 patients randomized, but then they extended the recruitment to include the 200 patients where they use FLOT as the chemotherapy backbone. And again, they randomized with or without pembrolizumab.
And then there’s another ongoing study of FLOT with or without a PD-L1 antibody development, which is called Matterhorn study. But that study is still recruiting. So I think when these studies read out, we will see where the perioperative chemotherapy will be of use. But at ASCO this year, there’s a third study, which they are only recruiting short term outcomes so far. So we’re not really going to see survival results. So that has been presented by Dr Salah-Eddin Al-Batran in the oral presentation at ASCO this year, where they look at the DANTE study which again, look a perioperative chemotherapy with, or without a PD, one antibody atlizumab. So I think we’ll of course be very pleased to hear those results. And then we’ll in due course hear the survival results from all these big randomized studies.
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