Reduced dosing of lenvatinib with pembrolizumab for advanced endometrial cancer

Objective

Evaluate safety and effectiveness of reduced lenvatinib doses with pembrolizumab in patients with mismatch repair-proficient (MMRp) advanced endometrial cancer.

Methods

In this retrospective cohort study of lenvatinib-pembrolizumab combination therapy, patients were grouped based on initial lenvatinib dose: 20 mg daily (Group 1), less than 20 mg daily (Group 2), and 20 mg daily five days per week (Group 3). The primary outcome was six-month progression-free survival (PFS-6); safety outcomes included incidences of lenvatinib dose discontinuation or reduction due to adverse events (AEs).

Results

This study included 369 patients (Group 1, n = 204, Group 2, n = 154, and Group 3, n = 11). There was no difference in PFS-6 between Groups 1 and 2 (40.2 % vs 33.8 % respectively; p = 0.26) or median PFS (both 4.2 months; p = 0.92). A significantly higher incidence in lenvatinib dose reduction was found in Group 1 (28.1 vs 14.3 per 100 person-year; p < 0.01). However, there was no difference in AE-related lenvatinib dose discontinuation between Groups 1 and 2 (7.2 vs 6.6 per 100 person-year, respectively; p = 0.61).

Conclusion

Full-dose lenvatinib has been associated with frequent dose modification without prospective data to guide optimization. We found no difference in PFS-6 or median PFS between starting doses of 20 mg daily versus <20 mg daily in combination with pembrolizumab. Fewer dose reductions were experienced with a lower starting dose. However, no difference in dose discontinuation was observed. These findings suggest lower initial lenvatinib doses may be better tolerated without compromising effectiveness, although the lower limit of effective dosing remains to be defined.