EP262 - Metastatic Colon Cancer and Single Agent Neoadjuvant Immunotherapy: A Single Institution Experience

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Purpose/Background: Pembrolizumab was granted accelerated FDA approval for the treatment of patients with metastatic MMR deficient solid tumors and has shown significant benefit in the treatment of metastatic colorectal cancer. Recently, the NICHE-2 trial demonstrated that neoadjuvant nivolumab plus ipilimumab led to a significant response in locally advanced MMR deficient colon cancer. This report is a single institution's experience regarding the treatment of metastatic colon cancer with neoadjuvant immunotherapy. Since 2022, our institution has treated two patients with neoadjuvant pembrolizumab for metastatic colon cancer and achieved complete clinical and pathologic responses with no residual evidence of malignancy. 

Patient A: 

A 43 year old female presented with an obstructing sigmoid colon mass on CT scan. Colonoscopy with biopsy confirmed well differentiated adenocarcinoma. Attempted resection was aborted when the mass was found intraoperatively to invade the uterus and left ovary, instead the patient was diverted. Post-operative PET demonstrated peritoneal carcinomatosis. Tumor biology testing demonstrated deficiency in MLH1 and PMS2.    

Patient B: 

A 53 year old male had positive fecal DNA testing and subsequent diagnostic colonoscopy confirmed a partially obstructing hepatic flexure mass, with biopsy proven adenocarcinoma. Staging scans demonstrated evidence of metastatic disease to the liver, level two cervical lymph nodes, left supraclavicular lymph node, and gastrohepatic and retroperitoneal lymph nodes. Nodal biopsy confirmed metastatic disease, and tumor biology testing revealed a loss of nuclear expression of PMS2 and MSH6 consistent with hereditary non-polyposis colorectal cancer (HNPCC) syndrome.

Methods/Interventions: Patient A was treated with pembrolizumab 200mg every three weeks for six cycles. Repeat PET CT showed significant improvement in distant activity but persistent disease within the sigmoid colon (Figure1). She then underwent chemoradiation and cytoreductive surgery with total abdominal hysterectomy, bilateral salpingo-oophorectomy and low anterior resection (LAR).

Patient B was treated with pembrolizumab dosed at 200mg every three weeks. Repeat imaging was done after four and sixteen months of treatment. He continues to receive immunotherapy every three weeks.

Results/Outcomes: Patient A: Surgical pathology showed complete pathologic response. The patient remained on maintenance immunotherapy. Endoscopic and radiographic surveillance have continued to show no evidence of disease.

Patient B: After four months of immunotherapy (March 2023), repeat PET demonstrated almost complete resolution of the previously known metastatic disease with minimal residual activity in one gastrohepatic lymph node and no activity at the site of the primary tumor. Repeat PET after sixteen months (March 2024) demonstrated a complete response (Figure1). He continues to receive immunotherapy every three weeks.

Conclusion/Discussion: We present two cases of metastatic colonic adenocarcinoma where complete responses were achieved using primarily neoadjuvant immunotherapy. This is consistent with other colon and rectal cancer studies that have demonstrated a benefit of immune checkpoint therapy specifically with MMR deficient or MSI-high tumor biology.  Our experience supports the benefits of neoadjuvant pembrolizumab in the pursuit of achieving complete clinical and pathologic responses in patients with metastatic MMR deficient colon cancers.