From the FDA Drug Label
Microsatellite Instability-High or Mismatch Repair Deficient Cancer for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
The patient has Stage III pT4 pN1 Duodenal cancer with MMR deficient status. Based on the information provided in the drug label, pembrolizumab (IV) can be used to treat MMR deficient solid tumors. Therefore, pembrolizumab can be considered as a treatment option for this patient. 1
From the Research
Yes, Stage III pT4 pN1 duodenal cancer with MMR deficient (dMMR) status should be treated with adjuvant immunotherapy rather than traditional chemotherapy. The recommended regimen is pembrolizumab (Keytruda) 200 mg IV every 3 weeks or 400 mg every 6 weeks for approximately 1 year (up to 18 doses) 2. This approach is based on the tumor's MMR deficiency status, which indicates high microsatellite instability (MSI-H) and creates a favorable environment for immunotherapy response. Patients with dMMR tumors typically have higher mutational burden, leading to more neoantigens that can be recognized by the immune system when checkpoint inhibitors like pembrolizumab are used. Before starting treatment, patients should undergo baseline thyroid function tests, liver function tests, and screening for autoimmune conditions, as immune-related adverse events are possible. Regular monitoring during treatment is essential. This immunotherapy approach has shown superior outcomes compared to traditional chemotherapy for dMMR tumors, with better response rates and improved disease-free survival in this specific molecular subtype of duodenal cancer. Some studies suggest that adjuvant chemotherapy may also be beneficial in stage III MSI-H/dMMR CRC, with a significant overall survival improvement 2. However, the use of pembrolizumab in combination with chemotherapy is being investigated in ongoing trials, such as the KEYNOTE-859 study 3. In the context of duodenal cancer, the evidence is limited, but the principles of immunotherapy in dMMR tumors can be applied, and pembrolizumab has been shown to be cost-effective in the treatment of unresectable or metastatic MSI-H/dMMR colorectal cancer 4. The National Comprehensive Cancer Network guidelines recommend resection and adjuvant chemotherapy for patients with locally advanced duodenal adenocarcinoma, but the use of immunotherapy is not yet established in these guidelines 5. A new classification system for duodenal adenocarcinoma has been proposed, which takes into account the pT4 and pN2 statuses, and may help to identify patients who require more intensive adjuvant treatment 6.
Key considerations for treatment include:
- The tumor's MMR deficiency status and high microsatellite instability (MSI-H)
- The potential benefits of adjuvant immunotherapy with pembrolizumab
- The need for regular monitoring and screening for autoimmune conditions
- The potential for improved overall survival and disease-free survival with immunotherapy
- The ongoing investigation of pembrolizumab in combination with chemotherapy in clinical trials.