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ESMO GI 2025 | Evaluating the potential of immunotherapy in dMMR/MSI-H CRC
Rocio Garcia-Carbonero, MD, PhD, University Hospital 12 De Octubre, Madrid, Spain, comments on mounting evidence that earlier treatment with immunotherapy is more effective in patients with dMMR/MSI-H colorectal cancer. Trials such as those involving dostarlimab, like AZUR-2 (NCT05855200), have shown maintenance of high levels of complete response in those previously treated with chemotherapy, radiotherapy, and surgery. This has major implications for quality of life, avoiding permanent colostomies and treatment-related toxicities. Although longer follow-ups and larger cohorts are needed to confirm curative outcomes, these approaches are already included in some clinical guidelines and are on the path to EMA approval. This interview took place at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancer 2025 Congress in Barcelona, Spain.
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Transcript
There is an increasing evidence of the fact that immunotherapy has greater efficacy in the earlier stage of disease. So we have growing evidence first from locally advanced rectal cancer with dostarlimab. The AZUR-2 trials have shown really incredible, a high complete response rate in these patients that were traditionally treated with chemotherapy, radiotherapy, and also very radical surgery that has major implications in patients’ quality of life, particularly if it even implies a live colostomy...
There is an increasing evidence of the fact that immunotherapy has greater efficacy in the earlier stage of disease. So we have growing evidence first from locally advanced rectal cancer with dostarlimab. The AZUR-2 trials have shown really incredible, a high complete response rate in these patients that were traditionally treated with chemotherapy, radiotherapy, and also very radical surgery that has major implications in patients’ quality of life, particularly if it even implies a live colostomy. So in this dostarlimab trial, the response rates are so high and with more follow-up, we see they are sustained in time and avoiding all these standard of care procedures that are really more toxic and a lot more cumbersome for patients. So of course we need more, a higher number of treated patients and on the follow-up to see whether this means cure of a high proportion of these patients or not. We still need to be a bit cautious on this, but certainly it is already included in clinical guidelines, not only in US guidelines, also in ESMO guidelines recently. And this is very important for patients, not yet approved though by EMA, but I think it’s certainly a strategy that deserves to be approved with current data. And we’ve had now also some recent updates of the first proof of concept trial by Luis Diaz in the three cohorts of two MSI and one MSS cohort. With 10 years follow-up, they show that complete responses really are sustained in time in that late relapses are really exceptional. So these are really very good news for our patients. And this can be also extended to colon cancer locally advanced. Of course, in this setting we have less data or less mature, but the NICHE trial shows how a very high proportion of complete or major pathological responses and well, it brings up a little bit the increase, the difficulty of assessing properly complete response, clinical complete responses, when you don’t have a pathological specimen in order to be able to avoid the surgery. So there’s a lot of work going on in this field and it’s really very exciting for our patients and it’s certainly going to change the standard of care, that’s for sure.
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