A 48-year-old woman with Stage IVB endometrial carcinoma (metastatic to lung and liver) has tumor tissue showing mismatch repair deficiency (dMMR) on immunohistochemistry. She progresses after first-line carboplatin-paclitaxel. What is the MOST appropriate second-line therapy with BEST evidence?
- A Medroxyprogesterone acetate 200 mg/day (hormone therapy)
- B Lenvatinib plus pembrolizumab combination
- C Pembrolizumab monotherapy (anti-PD-1 checkpoint inhibitor) ✓
- D Paclitaxel monotherapy with dose reduction
Explanation
For dMMR/MSI-high endometrial cancer progressing after platinum-based chemotherapy, pembrolizumab monotherapy has FDA approval (KEYNOTE-158 trial, 2021) with objective response rates of 48% and durable responses. The mismatch repair deficiency leads to microsatellite instability and high neoantigen burden, making these tumors exquisitely sensitive to PD-1 checkpoint blockade. Lenvatinib plus pembrolizumab (KEYNOTE-146/Study 111) is approved for all-comer endometrial cancer progression but is particularly effective in NSMP/MMR-proficient tumors as a combination. For dMMR tumors specifically, pembrolizumab monotherapy is preferred as it is less toxic and highly effective. Hormone therapy has low response rates in dMMR high-grade tumors.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.