Complete response to BRICS in Locally advanced pancreatic cancer (pMMR, CPS 30): a case report

Locally advanced pancreatic cancer (LAPC) has a dismal prognosis, marked by an exceedingly low 5-year survival rate. While immune checkpoint inhibitors (ICIs) have demonstrated efficacy across various solid tumors, their application in the treatment of pancreatic ductal adenocarcinoma-particularly in mismatch repair-proficient (pMMR) cases-is restricted by the immunosuppressive nature of the tumor microenvironment (TME). Thus, more effective treatment strategies for pMMR LAPC are urgently needed.

We present a 65-year-old female diagnosed with LAPC (cT4N1M0, Stage III), confirmed pathologically as pancreatic ductal adenocarcinoma with pMMR status and a high programmed death-ligand 1 (PD-L1) combined positive score (CPS) of 30. Initial tumor markers were significantly elevated (CA19-9: 62,228.8 U/L; CEA: 100 ng/mL). The patient received a novel multimodal treatment referred to as the BRICS Regimen, an acronym derived from Bifidobacterium supplementation, Radiotherapy (hypofractionated), Immunotherapy (PD-1 inhibitors), Chemotherapy (low-dose), and Stereotactic approach. This protocol can be modified to match the individual disease characteristics. In this case, the treatment comprised SBRT 24 Gy/3 fractions → q21d toripalimab 240 mg + nab-paclitaxel 200→100 mg + anlotinib 12 mg d1-14, with continuous Bifidobacterium triple viable tablets. Imaging following treatment indicated a complete response (CR), and tumor markers remained normal for 5 months post-therapy. The treatment was well tolerated, with no severe adverse events reported.

This report suggests that a combined modality approach-integrating SBRT, chemotherapy, antiangiogenic therapy, ICI, and probiotics-may achieve CR in patients presenting with pMMR LAPC and high PD-L1 expression, even without surgery. These results challenge the prevailing assumption that pMMR status invariably predicts resistance to immunotherapy. These findings suggest that, in pMMR pancreatic cancers with high PD-L1 CPS, multimodal treatment strategies may remodel the tumor microenvironment and overcome immune resistance, highlighting a promising therapeutic direction.