- Regardless of microsatellite instability (MSI), PD-L1 status, or histology, deep and durable responses were seen with lenvatinib plus pembrolizumab in patients with advanced endometrial cancer that had progressed under prior therapy.
- The combination was granted accelerated approval for nonMSI-H endometrial carcinoma by the FDA, the Australian Therapeutic Goods Administration, and Health Canada simultaneously on September 17, 2019.
Why this matters
- Pembrolizumab has been approved as monotherapy following treatment failure in endometrial cancer with high MSI only.
- Keynote-146/Study 111 was designed to evaluate the oral multikinase inhibitor lenvatinib with pembrolizumab in patients with advanced tumours.
- An interim analysis that included 53 patients has been published and reported a high overall response rate regardless of MSI status.
- Open-label, single arm.
- 20 mg/day lenvatinib oral plus 200 mg Q3W i.v.
- Primary endpoint objective response rate (ORR) at week 24.
- 108 patients, 11 with MSI-H.
- Funding: Eisai and MSD.
- ORR for total population at week 24: 41% as judged by investigators. 44% when assessed in independent imaging review.
- Median duration of response 21.2 months (investigator) and 31.4 months (independent through imaging).
- Median PFS total 7.5 months, MSI-H 18.9 months, nonMSI-H 5.4 months.
- Median OS total 16.7 months.
- Treatment-related adverse events were frequent and led to study-drug interruptions in 72% of patients, dose reductions in 65%, and discontinuation in 19%.
- No control arm, but a phase 3 trial of lenvatinib plus pembrolizumab versus doxorubicin or weekly paclitaxel is ongoing.
- “The benchmark for this type of cancer is 15% [and we’ve now seen] unprecedented results. The bad thing is that toxicity was as remarkable as activity,” said Nicoletta Colombo, University of Milan-Bicocca, who was not involved in the study.