Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer

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Published: 22 Oct 2018
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Dr Myriam Chalabi - Netherlands Cancer Institute, Amsterdam, Netherlands

Dr Myriam Chalabi speaks with ecancer at ESMO 2018 in Munich about the first neoadjuvant study of anti-CTLA-4 ipilimumab plus anti-PD1 nivolumab in early stage dMMR and MMR proficient colon cancers.

She links mismatch repair status and response rates observed in 15 tumours, and describes the tolerability as a positive indicator for further research in neoadjuvant immunotherapy for these patients.

Combination immunotherapy for metastatic colorectal cancer (mCRC) is also discussed by Dr Heinz-Josef Lenz here.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

Today we presented the first results of the NICHE study which stands for neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. This is a first in kind study so this has never been done before. What we saw is that in patients with dMMR tumours, so the MMR deficient colon cancers which comprise around 15% of early stage colon cancers, we saw 100% major pathological responses. That was very impressive; we expected these patients to respond but we did not think that these tumours would disappear in four weeks’ time in all patients. Also in the MMR proficient tumours we saw that these tumours were responding in the sense that in the tumour microenvironment we were seeing changes. So we’re seeing increased infiltration of CD8 T-cells, we’re seeing increased TCR clonality, however these tumours are not responding as well as the dMMR tumours are but we do not know what would have happened if we would have waited a bit longer, for example, in these tumours.

We included 14 patients in the presentation, we have 19 patients included total now. Of those 14 patients we had 7 dMMR tumours and 8 pMMR tumours and that’s because one patient had a double tumour so the addition is correct, it’s 15 tumours.

When it comes to their tolerance of the treatments, how well did it go down?

That went very well, the treatment was deemed safe. So all patients received both planned treatment doses. They all underwent timely resection of their tumour, radical resection of the tumours, and we saw very few grade 3 adverse events – two pre-operative adverse events, one of which was actually due to pseudo-progression so this patient had a complete response but had an adverse event due to that. Three adverse events were post-operative and all of them were deemed to be due to the surgery and not to the immunotherapy. So this treatment was safe and very feasible.

Have you seen anything that has been found in some other cases of using checkpoint immunotherapy where the stronger the reaction, the stronger the adverse events, the more duration there is in response?

So we were very glad that that was not the case with regards to the adverse events in our population. We saw a very strong reaction but we did not see that back in the adverse events in this patient population. So we’re hoping that this will be the case for all patients treated in the neoadjuvant setting with low dose ipilimumab. We have to remember that this is a very short-term treatment so they only receive two treatment doses but maybe that’s enough.

Are there any plans for expansion to see what happens with different patients, more patients, more drug?

Yes, we’re still including patients, the trial is ongoing and we hope to be able to give an update soon on what is happening in the pMMR tumours but also if we continue to see these fantastic responses in the dMMR tumours which we have very good hopes for that would be the case.

This is the first time this has been shown in early stage colon cancers and the fact that we’re seeing major pathological responses in all dMMR tumours makes that these data have the potential to be practice-changing. As our discussant also talked about, this may be the future of these patients with dMMR tumours. So let’s hope that we can see that happen.

If I could also ask for just a quick comment on how this research fits in to the other research presented by Dr Lenz, I think it is.

That is in patients with metastatic disease who have not received prior treatment for their metastases. What we see there is that the response rates increase compared to when you treat heavily pre-treated patients which they have published before. So now we see that if you move it up you see more responses; the overall survival data still have to come in but that is very encouraging and that is in line with what we are seeing that if you give the treatment earlier you have better responses.

So checkpoint inhibitors for colorectal cancer showing promise then.

Definitely for dMMR colorectal cancers; for the pMMR tumours we have hope, we’re seeing things happen, but we just need to find out what this means exactly and how we can improve if it needs improvement. That will be in the future.

Well we look forward to hearing more from you as that comes out then.

Perfect. Thank you.