A group of authors from the Memorial Sloan Kettering Cancer Center, New York, NY, US, performed a systematic review to investigate the association between the duration of neoadjuvant immunotherapy in patients with localised mismatch repair-deficient (MMRd) tumours and the rate of complete response to immune checkpoint inhibitors (ICIs).
A longer duration of ICI therapy is associated with a higher rate of complete response among patients with MMRd cancers according to Dr. Luis A. Diaz and colleagues, who published the findings on 19 February 2025 in The New England Journal of Medicine.
Neoadjuvant treatment duration for MMRd colorectal cancer with anti-PD1 therapy alone ranged from 1 to 7 months and resulted in complete response ranging from 0 to 100%. The authors performed a probit model-fitting analysis, which showed a positive association between treatment duration and rate of complete response (p < 0.001; p = 0.08 for testing for goodness of fit) among patients with nonmetastatic colorectal cancer.
A combination of anti-PD1 and anti-CTLA4 therapy in the neoadjuvant setting for MMRd colorectal cancer used treatment duration of 1.5 months or less to mitigate toxicity. This combination resulted in complete response ranging from 68% with 4 weeks of treatment to 80% with 6 weeks of treatment. It would be expected that a longer treatment duration would lead to a higher rate of complete tumour ablation.
The authors commented that organ preservation after a clinical complete response to neoadjuvant immunotherapy alone or combined with chemotherapy seems safe and has excellent outcomes. Optimising the duration of neoadjuvant immunotherapy alone or in combination with cytotoxic or targeted therapy may lead to effective strategies to maximise the number of patients who benefit from nonsurgical immunoablative approaches and may provide insights into the minimum duration of treatment in adjuvant and metastatic settings.
This work was supported by Swim Across America, the Simon and Eve Colin Foundation, the Dalton Family Foundation, the American Association for Cancer Research–Stand Up To Cancer Colorectal Cancer Dream Team, and the National Cancer Institute of the US National Institutes of Health.
Reference
Rousseau B, White JR, Cercek A, Diaz LA. The Duration of Immunotherapy for Mismatch Repair–Deficient Cancers. N Engl J Med 2025;392:824-826.