A novel approach using a combination of nivolumab and ipilimumab has led to a pathological complete response (pCR) in a 24-year-old male patient with advanced, metastatic deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) colon cancer. The case, detailed in a recent report, demonstrates the potential of dual immune checkpoint inhibitors (ICIs) in converting initially unresectable tumors into resectable ones, offering a promising strategy for managing advanced colorectal cancer.
The patient, who presented with a large tumor invading the right ureter, duodenum, and inferior vena cava, along with multiple pulmonary metastases, initially underwent neoadjuvant chemotherapy with capecitabine, oxaliplatin, and bevacizumab. However, the tumor progressed, prompting the use of nivolumab (240 mg) plus ipilimumab (1 mg/kg) every three weeks. After three courses, the tumor remarkably shrank, and the pulmonary metastases disappeared. Following additional nivolumab monotherapy, surgical resection was performed, revealing a pCR.
Immunotherapy as First-Line Treatment
The success of this case raises the question of whether immunotherapy should be considered as a first-line treatment for dMMR/MSI-H metastatic colorectal cancer (mCRC). The KEYNOTE-177 trial demonstrated a high complete response rate for pembrolizumab as a first-line treatment in this patient population (11% vs. 3.9%). The synergistic action of nivolumab and ipilimumab, promoting T-cell antitumor activity through complementary mechanisms, may explain the observed efficacy.
Optimal Immunotherapy Duration and Timing of Surgery
Determining the optimal duration of ICI therapy and the timing of surgical resection remains challenging due to limited data. In this case, surgery was performed four weeks after the last nivolumab infusion. The risk of local regrowth and distant metastases needs to be carefully balanced against the potential benefits of continued immunotherapy.
Challenges in Assessing Tumor Response
Radiological assessment of tumor response to immunotherapy can be difficult, with phenomena like pseudoprogression potentially complicating treatment decisions. Conventional assessment methods based on tumor size may not accurately reflect the treatment effect of ICIs. Advanced imaging modalities, such as PET-CT, may be useful in distinguishing pseudoprogression from true tumor progression.
Implications for Clinical Practice
This case report provides valuable insights into the use of immunotherapy in the conversion setting for advanced colorectal cancer. While further research is needed to confirm these findings, the results suggest that initial immunotherapy could be considered as a standard management protocol for dMMR/MSI-H mCRC in conversion settings. The successful resection of an initially unresectable metastatic colon cancer, achieving pCR after dual ICI therapy, highlights the potential of this approach to improve outcomes for patients with advanced disease.
