“In the NICHE-2 study, two cycles of neoadjuvant nivolumab plus low-dose ipilimumab led to unprecedented pathologic responses in patients with MMR deficient colon cancers.” said study lead author Myriam Chalabi, NKI - Netherlands Cancer Institute, Amsterdam, Netherlands.
“At baseline, a significant proportion of patients had radiological stage III and high-risk disease. The expected disease recurrence rate for (pathologic) stage III dMMR tumours is between 20-40% despite standard-of-care adjuvant chemotherapy. However, to date, none of the patients from NICHE-2 have had recurrence of disease. Importantly, this treatment was very well-tolerated, with only 4% grade 3-4 immune-related adverse events and no unexpected surgical complications. NICHE-2 provides the backbone for organ-sparing treatment of dMMR colon cancers after neoadjuvant immunotherapy.”
“This study explores the role of a very active “short course” of preoperative immunotherapy and questions the need of surgery and postoperative chemotherapy in all patients in whom the primary tumour has disappeared.” Commented Andrés Cervantes, INCLIVA Biomedical Research Institute, Hospital Clínico Universitario, University of Valencia, Valencia, Spain, not involved in the study.
“Standard of care for the treatment of localised colon cancer with deficient Mismatch Repair status (dMMR) consists in surgical resection followed by adjuvant chemotherapy, despite the fact that chemotherapy is not so active and a complete disappearance of the tumour in the surgical specimen is not observed with chemotherapy." In this study, Chalabi and colleagues used a very innovative approach, consisting in a very short course of preoperative immunotherapy followed by surgical resection.
“dMMR behaves as strong predictor of the positive effect observed with this short course immunotherapy and determining dMMR can be easily done by immunohistochemistry in the conventional pathology lab without the need of complex molecular testing. Finally, the minimal toxicity observed may also facilitate the implementation of this strategy, potentially sparing patients from surgery," Cervantes concluded.