However, standard practice has changed since the studies which formed the backbone of ATOMIC's analysis.

The NICHE trials showed remarkable response to treatment with only a few doses of immunotherapy before surgery.

www.nejm.org/doi/full/10....

2-year recurrence rates were 0% (!!)

ATOMIC demonstrated that adding immunotherapy to this standard chemotherapy further reduced recurrence rates for stage III CC when given after surgery.

This is fundamentally practice changing IF we were routinely utilizing surgery followed by chemotherapy for stage III dMMR CRC

Colon cancers that are mismatch repair deficient (dMMR) are both responsive to immunotherapy and not particularly responsive to chemotherapy.

This meta-analysis showed chemo gave a small but statistically significant improvement in survival in stage III CC (pmc.ncbi.nlm.nih.gov/articles/PMC...)

Concurrent durvalumab given with FLOT, followed by durvalumab maintenance in the post-operative setting led to an impressive improvement in disease-free survival over an already impressive baseline from the ESOPEC study.
(www.nejm.org/doi/full/10....)

For adenocarcinomas, ESOPEC dethroned these results. Giving aggressive chemotherapy (FLOT) resulted in outcomes numerically comparable to the chemoradiation + immunotherapy from the CheckMate 577 study, but with the benefit of statistical significance.
(www.nejm.org/doi/full/10....)

However, the OS data from that study have only trended to improvement. This may be accounted for by the relatively high (-ish?) baseline survival numbers, but is still disappointing. (Abstract 4000, ASCO 2025)

BRAF-targeted therapies plus chemotherapy IS the new standard-of-care for treatment of these cancers. It has been the practice at our center since the original publication of these data in Nature in January.

#ASCO25 #OncSky

This is despite nearly 72% of the patients in the standard-of-care group getting targeted therapy on progression with chemotherapy.