Treatment with checkpoint inhibitors for unresectable non-metastatic mismatch repair deficient intestinal cancer; a case series.

Background: Colorectal cancer (CRC) is a common malignancy, with mismatch repair deficient (dMMR) CRC comprising approximately 15% of non-metastatic cases. dMMR tumors generate neoantigens making them highly responsive to immune checkpoint inhibitors, this became the first-line treatment for metastatic dMMR CRC. Aim of this study is to evaluate the efficacy of single-agent Pembrolizumab for patients with locally advanced unresectable dMMR intestinal cancers.

Methods: We retrospectively reviewed patients with locally advanced unresectable dMMR/MSI-H CRC or small intestinal adenocarcinoma (SIA) who received PD-1 inhibitors between January 2022 and December 2023 at 1 University Medical Center and 3 regional hospitals and analyzed the treatment efficacy and survival outcomes.

Results: Response rate was 78% after at least one cycle of Pembrolizumab with conversion to resection in nearly 40%. Patients who underwent primary tumor resection had a two-year overall survival (OS) of 100%, whereas those without resection had significantly lower OS (42%), progression-free survival (PFS; 36%), and cancer-specific survival (CSS; 71%) at two years. In total, 22% of the patients discontinued the treatment due to toxicity.

Discussion: Although the observed response rates of Pembrolizumab are high, there is still room for improvement. Dual immune checkpoint inhibitors might be needed for these patients to improve outcomes.

Clinical trial registration: A selection of patients included in this study were part of the ATAPEMBRO study, a single-centre, open label, phase 1-2 study (NCT04014530).