- Combination of lenvatinib and pembrolizumab showed activity in phase 1b/2 trial of advanced urothelial cancer patients.
Why this matters
- Urothelial cancer accounts for >90% of bladder cancers.
- Tyrosine kinase inhibitors such as lenvatinib, which has shown activity in urothelial cancer, may reverse immunosuppressive environment that results in immunotherapy failure.
- Findings suggest further investigation of lenvatinib+pembrolizumab in this setting.
- Phase 1b/2 multicenter, open-label study.
- Metastatic urothelial cancer patients received lenvatinib 20 mg/day orally + pembrolizumab 200 mg/3 weeks intravenously.
- Primary endpoint: Objective response rate (ORR) at week 24 based on immune-related RECIST (irRECIST).
- Funding: Eisai Inc.
- 20 patients enrolled at 3/1/2018 data cutoff.
- 11 and 5 patients had received 1 and 2 lines of prior anticancer therapy, respectively.
- None had received prior immunotherapy.
- ORR at week 24: 25% (95% CI: 8.7-49.1).
- Median PFS (based on irRECIST): 5.4 months (95% CI: 1.3-not estimable).
- Median follow-up for PFS: 11.7 months (95% CI: 2.7-17.7).
- 4 patients (3 still on study) remain in complete remission.
- 18 patients had >1 treatment-related adverse event (TRAE).
- Most common any-grade TRAEs: proteinuria, diarrhea, fatigue, hypertension, hypothyroidism.
- 1 fatal TRAE (gastrointestinal hemorrhage).