MATTERHORN is a phase III study that is designed to answer the question whether or not addition of perioperative durvalumab to FLOT therapy can improve outcomes and treat micrometastatic disease in patients with localised non-metastatic gastro-oesophageal adenocarcinoma.
What was the methodology?
MATTERHORN is a large phase III study, over 900 patients were randomised. Patients with localised non-metastatic gastric and GE junction adenocarcinoma, irrespective of PD-L1 status, were enrolled globally. We stratified patients for geographic location – Asia versus non-Asia – and advanced lymph node disease and lymph node status.
Patients were randomised in a 1:1 fashion to receive durvalumab with three-drug chemotherapy with FLOT versus placebo and FLOT. Patients received four cycles of perioperative neoadjuvant FLOT and two cycles of durvalumab. FLOT is given every two weeks, durvalumab is given every four weeks. Then patients were assessed for surgery and after surgery, if their surgery was successful and they recovered, patients had four additional cycles of FLOT if appropriate with up to nine additional cycles of durvalumab, so a whole year of therapy. They were followed for event free survival as a primary endpoint and the secondary endpoint of overall survival and pathologic complete response.
What did you find?
MATTERHORN, we’ve presented the interim analyses before and the first interim analysis looked at pathologic complete response. What we have shown is that pathologic complete response was clinically meaningfully improved and statistically significant between the addition of durvalumab versus placebo. So with the durvalumab FLOT cohort we saw 19% pathologic complete response, meaning complete pathologic assessment, no residual tumour in the primary tumour or the lymph nodes, versus 7% with FLOT durvalumab. This difference met the prespecified interim analysis and after that the alpha was passed to event free survival.
The event free survival analysis was triggered when at least 34% of patients had events, defined as either recurrence, progression or death. We did the event free survival analysis and, as you saw in the press release and can guess based on the fact that we’re selected for the ASCO plenary, this was a meaningful difference in event free survival that was demonstrated and suggests that MATTERHORN will set the new global standard for patients worldwide.
We’re also presenting data from overall survival which was a secondary endpoint of the study and we’ll presenting at ASCO plenary session.
Can you give us some information on any adverse events?
The most common side effects that we see, adverse events that we see, with FLOT durvalumab are related to chemotherapy. As you can imagine, three-drug cytotoxic chemotherapy with fluoropyrimidine, oxaliplatin, leucovorin and docetaxel can be quite taxing and the most common side effects are diarrhoea, nausea, vomiting and neutropenia. We did not see any new safety concerns in the study and this is an important highlight that this regimen is feasible for the global population of patients. This was a study enrolling patients worldwide, in the United States, North America, South America, Europe and Asia.
What could be the impact of these findings?
We’re hoping that we will help patients worldwide by bringing this new regimen to the clinic. We recognise that FLOT is the new accepted standard globally. Of course, it started in Europe and the United States and now has been adopted by many guidelines in South Korea and Japan, so demonstrating that immunotherapy can improve survival in these patients and that it’s feasible to give patients durvalumab and FLOT, will change the global standard and the patients will be able to get access to immunotherapy before surgery and before developing metastatic disease so that we can treat micrometastasis and supress this recurrence and prevent cancer recurrence and cure more patients.
Is there anything else you would like to add?
I want to thank our patients and their caregivers for their trust and their quiet victories along the way going through this regimen because it was a difficult, certainly, time in everyone’s life when we were enrolling patients during the global pandemic. If you’re familiar with the quote, this is what I’m going to use at the end of my presentation when I’m thanking the patients, from Taylor Swift: Long live all the mountains that we moved. I had the time of my life fighting dragons with you.
