- The FDA has granted accelerated approval to pembrolizumab+lenvatinib for the treatment of patients with advanced endometrial cancer who have disease progression after prior systemic therapy.
- The indication applies to patients who are not candidates for surgery or radiation and have disease that is not microsatellite instability-high or mismatch repair deficient (MSI-H/dMMR).
- Recommended dose: 20 mg oral lenvatinib once daily with pembrolizumab 200 mg every 3 weeks.
Why this matters
- Review decisions were simultaneous in the United States, Australia, and Canada under Project Orbis.
- The Real-Time Oncology Review (RTOR) pilot program allowed FDA data review before application submission.
- Approval was based on the single-group, open-label KEYNOTE-146 study of 108 patients with metastatic endometrial carcinoma who progressed after ≥1 prior systemic therapy.
- 94 patients did not have MSI-H or dMMR tumors:
- Objective response rate was 38.3% (complete responses, 10.6% and partial responses, 27.7%).
- Median duration of response was not reached; 69% of responders had response durations ≥6 months.
- Tumor MSI status was determined using a polymerase chain reaction test and MMR status, using an immunohistochemistry test.
- The most common adverse reactions (≥20%) were fatigue, hypertension, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, stomatitis, vomiting.