Combination Pembrolizumab and Lenvatinib in metastatic Mismatch Repair Deficient Adenocarcinoma of Mullerian Origin: A Case Report

Background For mismatch repair protein deficient (dMMR) endometrial cancer (EC), first line therapy remains platinum-based chemotherapy. For dMMR EC that has progressed on standard first line platinum containing chemotherapy, treatment with programmed death ligand-1 (PD-1) inhibitors such as Pembrolizumab have become integral to second line therapy. The challenging question remains, however, what the next best step is when these treatments fail. Case Here we report the case of a 71-year-old female who developed disease recurrence more than 20 years after surgical treatment for early stage dMMR endometrioid EC, with subsequent progression of disease on second line Pembrolizumab therapy; however displayed excellent response to third line treatment with Lenvatinib and Pembrolizumab. Conclusion Consensus regarding third line treatment for patients with dMMR EC who progress on single agent PD-1 inhibitors after platinum-based chemotherapy failure remains unclear. While single agent Pembrolizumab has demonstrated the greatest efficacy for dMMR disease, this case demonstrates a patient who had progression of disease on single agent Pembrolizumab, however had excellent response with combination Pembrolizumab and Lenvatinib. Further study is warranted to assess the efficacy of this regimen for advanced or recurrent dMMR EC.