Neoadjuvant immunotherapy for nonmetastatic dMMR/MSI colon cancer: a real-world retrospective AGEO study.

BACKGROUND

Several studies showed that in mismatch repair-deficient (dMMR)/microsatellite instability (MSI) nonmetastatic colon cancer (CC), neoadjuvant immune checkpoint inhibitors (ICIs) were associated with exceptional rates of pathological major response (pMR) and complete response (pCR). Patients included in these trials, however, were highly selected, and real-life data are now needed to better evaluate the efficacy and tolerability of neoadjuvant ICIs in routine clinical practice.

PATIENTS AND

METHODS

This retrospective observational study aimed to describe the clinical practices regarding ICIs in the neoadjuvant setting for patients with dMMR/MSI nonmetastatic CC, and to evaluate their efficacy and safety in real-world conditions. Patients receiving ICIs as part of a therapeutic trial were excluded.

RESULTS

Between 2019 and 2024, 32 patients were included across six French centers [median age 70 years (range 51-76 years), Lynch syndrome 31%]. Twenty-four patients had right-sided CC (85%), including three (9%) with two primary tumor locations. Ten patients (31%) received ipilimumab + nivolumab (NICHE regimen), while 22 (69%) were treated with pembrolizumab monotherapy. Grade ≥3 toxicities were observed in six patients (19%), including one toxic death and three toxicities (9%) leading to treatment discontinuation (one rheumatoid polyarthritis-like syndrome and two tumor fistulizations). Three patients developed bowel obstruction while receiving ICIs, two of whom underwent surgery showing pCR and pMR. Thirty patients were resected and 33 tumors were analyzed histologically with pMR in 21 cases (64%) including pCR in 14 cases (42%). The presence of an independent-cells contingent was statistically associated with poor pathological response.

CONCLUSIONS

This retrospective real-world study confirms the excellent results of neoadjuvant ICIs in dMMR/MSI nonmetastatic CC patients. pMR and pCR rates were, however, lower than those published in previous studies (64% and 42%, respectively), with higher rates of grade ≥3 toxicity, including one potential toxic death and three treatment discontinuations.