The DESTINY-Gastric02 study is a very important study because it’s the first study in western patients with HER2 positive Gastric or Gastroesophageal junction adenomas who were progressive on trastuzumab containing chemotherapy. And then, the patients were treated with the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhurtu). This was a study Western in patients and it’s following the Gastric01 study, which was in Asian and Korean patients.
This Gastric02 study was a phase two study. It’s a nonrandomized study and the primary endpoint. Is response rate objective response rate as evaluated by independent committee responses are important in this situation because this is in second-line. These were all patients who were progressive on the first-line treatment in this situation.
And then another important aspect on specificity of the Gastric02 study is that this study was run, was ongoing. Impatience with all HER2-positive tumors. With that, we checked before we included a patient again, the, HER2 status. And that’s indeed important because we know that after progression on first-line treatment with trastuzumab containing regimen.
Up to 30% of patients may lose over HER2 expression. So this study was therefore very pure with this inclusion criteria. The study was a positive study meaning that we saw quite a lot of responses, 38 patients out of 79. Or 30% of the patients had an objective tumor response according to the racist criteria and also looking at the waterfall plots, it shows that many patients had tumor regression.
And the third important aspect is that those patients with the response, and usually a quite long response, indeed the response duration was over eight months, the medium response duration, which is more than what we usually see in many of the second line studies in yesterday.
The side effect profile with fam-trastuzumab deruxtecan-nxki (Enhurtu) was quite good. It was quite okay. There were no new surprises, no new findings. The median treatment duration was over four months in these patients, the most. Common drug-related, adverse events associated with treatment. Discontinuations were pruritus and ID and pruritus, and ID was present in six patients or 8%.
One patient had grade 5, and the other patients had a grade 1 or 2. ID there were no. Trees have force and immediate time to onset of ID pruritus was 80 days. So almost three months with a million duration of over one month 38 days. And then looking at some of the other adverse events the most.
Common adverse events associated with dose reduction were nausea 8% and decreased neutrophil count was 5%. So, as you can see, it is not very frequent. And that’s also seen when we look at the great trees or more at adverse events. They’re not very frequent. So
This study is important indeed. Destiny02 study together with the destiny or one study, which was run in Japan and Korea, show that trastuzumab is an active agent in pretreated patients with HER2 positive metastatic or de junction adenocarcinomas who were progressive while on trastuzumab containing regimen.
And indeed in the agent study, there was an improved survival with. Can compare to chemotherapy of choice by physicians. And then in this Western study with a 38% response rate which is high in this population in second (inaudible) cancer we can say that this is a new standard of care and new reference regimen.
And that’s why also the Japanese authorities and the FDA have approved this agent in pretreated patients with HER2 positive (inaudible) of the stomach (inaudible).
(inaudible) scan is active. This gives, of course, opportunities to further do new studies. And there are some studies going with different combinations with fam-trastuzumab deruxtecan-nxki (Enhurtu) combination studies with other cytotoxics. For instance, these are early dose-finding studies in first-line. That’s important.
In second line, there is also another randomized study ongoing for regions like Europe where fam-trastuzumab deruxtecan-nxki (Enhurtu) is not yet approved. And that’s the DESTINY-04 study. And this study. Patients are randomized between fam-trastuzumab deruxtecan-nxki (Enhurtu) and compared to paclitaxel (inaudible) map. I’m confident that we will see nice results in this study, and it’s important because a whole field is opening.
We also see some other HER2 targeted agents coming through, but the antibody, the field of antibody-drug conjugate, is really important. In this setting, we have, of course further to understand the exact strategy, but already right now, based on this Asian phase 2 and this Western phase 2 study, we can say that there is a new reference treatment for these.
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Professor Eric Van Cutsem, MD, Ph.D., is a full professor and Division Head of Digestive Oncology at the University of Leuven (KUL) and University Hospitals Gasthuisberg, Leuven, Belgium. In this interview, Professor Van Cutsem speaks about Comments on the DESTINY-Gastric02 trial from Enhertu.
Brief Synopsis:
Participants with stomach or gastroesophageal junction cancer will be enrolled in this trial to see if trastuzumab deruxtecan is safe and effective.
They must have stomach or gastro-esophageal junction (GEJ) cancer that is human epidermal growth factor receptor 2 (HER2) positive:
* that cannot be surgically removed
* that has spread throughout the body
* that deteriorated during or during trastuzumab treatment
A total of 80 people will be enrolled in the study. North America and the European Union will host sites.