title: Pathological complete response with anti-PD-1 therapy in a patient with microsatellite instable high, BRAF mutant metastatic colon cancer: a case report and review of literature.
abstract: Mismatch repair (MMR) and BRAF mutation status are established independent prognostic factors for colorectal cancer (CRC). MMR deficient tumors are considered to have better prognosis whereas BRAF mutation is associated with poor prognosis. Studies evaluating the combined effect of BRAF and MMR status suggest MSI-high and BRAF mutant patients have a poorer prognosis as compared to MSI-high and BRAF wild type patients. Emerging evidence suggests MMR status predicts the immune response to anti-PD-1 therapy in CRC patients; however little is known about combined MMR and BRAF mutation status in this context. Therefore, it is important to identify whether there is a differential response to anti-PD-1 therapy based on BRAF status in the subset of MSI-high CRC patients.
  
  
  
  We report the first case of MSI-high, BRAF mutant metastatic CRC that had an excellent response (pathologic complete response) to anti-PD-1 therapy. We take this opportunity to review the similar cases in literature and discuss combined MMR and BRAF status as a potential biomarker for anti-PD-1 therapy.
  
  
  
  The case presented illustrates that anti-PD-1 therapy can be effectively used to treat CRC patients with MSI-high and BRAF mutant status which is usually considered a poor prognostic category as opposed to MSI-high and BRAF wild type tumors. Future studies with anti-PD-1 therapy distinguishing these molecular subgroups will improve our knowledge of whether BRAF status can add to MMR status as a predictive biomarker for anti-PD-1 therapy in patients with metastatic CRC.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Amikar
authors.initials: A
authors.lastname: Sehdev
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Harvey M
authors.initials: HM
authors.lastname: Cramer
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Ashley A M
authors.initials: AA
authors.lastname: Ibrahim
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Younger
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Bert H
authors.initials: BH
authors.lastname: O'Neil
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D000068818:Cetuximab / Q000008:administration & dosage / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D053843:DNA Mismatch Repair / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018714:Radiotherapy, Adjuvant; D066066:Response Evaluation Criteria in Solid Tumors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000068258:Bevacizumab; C582435:pembrolizumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000068818:Cetuximab; D005472:Fluorouracil