Real-World Analysis of Neoadjuvant Immune Checkpoint Inhibition for Patients With dMMR/MSI Nonmetastatic Colon Cancer
According to results from a retrospective, observational study, neoadjuvant immune checkpoint inhibitors (ICIs) were effective and safe among patients with mismatch repair-deficient (dMMR) microsatellite instability (MSI) nonmetastatic colon cancer.
“Several studies showed that in mismatch repair-deficient/ microsatellite instability nonmetastatic colon cancer, neoadjuvant neoadjuvant immune checkpoint inhibitors were associated with exceptional rates of pathological major response (pMR) and complete response (pCR)... however, [patients] were highly selected, and real-life data are now needed to better evaluate the efficacy and tolerability of neoadjuvant ICIs in routine clinical practice,” stated Julien Taieb, MD, PhD, Georges Pompidou European Hospital, Paris, France, and coauthors.
In this study, researchers collected data from 32 patients treated across 6 institutions who underwent at least 1 cycle of either ipilimumab plus nivolumab (n = 10) or pembrolizumab monotherapy (n = 22). Patients receiving ICI therapy as part of a therapeutic trial were excluded from this analysis. The primary end point was pathological response. Key secondary end points included ICI tolerability, safety, recurrence-free survival (RFS), and overall survival (OS).
At the data cutoff point, 94% of patients underwent surgical resection with a median interval of 6.1 weeks between last ICI dose and surgery. Of the 33 tumors collected, pMR was achieved in 64%, including 42% of which achieved pCR. The pCR rate was 67% following treatment with ipilimumab plus nivolumab and 33% following treatment with pembrolizumab monotherapy. No statistically significant difference in tumor regression grade (TRG) was observed between treatment arms (P = .22). Poor response to ICI therapy was observed in 11 patients, with 12% of patients having TRG 4 and 100% viable tumor cells and 21% of patients having TRG 3. The presence of independent-cells contingent on the surgical specimen was associated with poorer response (P < .01) and was observed in 45% of poor responders. Following ICI, complete radiological response was observed in 14% of patients, all of which had pCR at surgical examination. Partial radiological response or stable disease was observed in 11 pCR tumors.
Grade ≥3 adverse events were observed in 6 patients and most frequently included arthritis, fistulization, and bowel obstruction. Adverse events led to treatment discontinuation in 3 patients (due to rheumatoid polyarthritis-like syndrome and tumor fistulizations). One death occurred due to hypoxic cardiorespiratory arrest.
“This study generates the first real-world evidence on preoperative ICI in MSI/dMMR nonmetastatic [colon cancer] patients and valuable insights into real-world prescribing practices and patient outcomes,” concluded Dr Taieb et al.
Source:
Lemaire C, Boileve A, Manceau G, et al. Neoadjuvant immunotherapy for nonmetastatic dMMR/MSI colon cancer: A real-world retrospective AGEO study. ESMO Open. Published online: July 31, 2025. doi: 10.1016/j.esmoop.2025.105516
