In an analysis reported as a letter to the editor in The New England Journal of Medicine, Rousseau et al found a relationship between the duration of neoadjuvant immunotherapy and the likelihood of pathologic complete response in patients with localized mismatch repair–deficient (MMRd) colorectal cancer.
Study Details
The study involved data from 13 trials of neoadjuvant PD-1 inhibitor therapy alone or combined with CTLA-4 inhibitor therapy in patients with MMRd colorectal cancer.
Key Findings
The duration of neoadjuvant treatment in patients receiving anti–PD-1 therapy alone ranged from 1 to 7 months, with incidence of complete response of 0 to 100%. An analysis to adjust for the broad range of durations of treatment showed an association between treatment duration and incidence of complete response (P < .001, P = .08 for testing for goodness of fit).
Patients receiving anti–PD-1 and anti–CTLA-4 therapy had treatment durations of ≤ 1.5 months, with the shorter duration, according to investigators, likely used to reduce toxicity. The rate of complete response ranged from 68% with 4 weeks of treatment to 80% with 6 weeks of treatment; as noted by the investigators, “[I]t would be expected that a longer duration of therapy would lead to a higher incidence of complete tumor ablation.”
The investigators stated: “A longer duration of neoadjuvant immunotherapy for locally advanced cancers may increase the incidence of complete response and open the door for organ-sparing strategies…. Optimizing the duration of neoadjuvant immunotherapy alone or in combination with cytotoxic or targeted therapy may lead to effective strategies to maximize the number of patients who benefit from nonsurgical immunoablative approaches and may provide insights into the minimum duration of therapy in adjuvant and metastatic contexts.”
Luis A. Diaz, Jr, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit nejm.org.
