Real-world clinical outcomes of lenvatinib+pembrolizumab for the treatment of patients with non-microsatellite instability-high/mismatch repair proficient recurrent or advanced endometrial cancer following prior systemic therapy in the United States

Abstract

OBJECTIVE: The Study-309/KEYNOTE-775 trial demonstrated significantly improved outcomes with lenvatinib plus pembrolizumab (lenvatinib+pembrolizumab) versus chemotherapy. Lenvatinib+pembrolizumab is recommended in the United States for patients with non-microsatellite instability-high/mismatch repair proficient advanced or recurrent endometrial cancer who have progressed following prior systemic therapy. We evaluated the comparative effectiveness and clinical outcomes of lenvatinib+pembrolizumab versus single-agent chemotherapy as second-line or later treatment in this population.

METHODS: This physician-led retrospective medical record review involved data extraction from records of eligible adult women in the United States with non-microsatellite instability-high/mismatch repair proficient advanced endometrial cancer who had progressed following previous systemic therapy and received lenvatinib+pembrolizumab or single-agent chemotherapy. Stabilized inverse probability of treatment-weighted analyses were used to compare real-world objective response rate, real-world progression-free survival, and overall survival.

RESULTS: Data were extracted for 97 patients treated with lenvatinib+pembrolizumab and 107 treated with single-agent chemotherapy (median age: 57.7 and 57.1 years at treatment initiation, respectively). Most patients were White (61.9%; 60.7%), diagnosed at stage IV (56.7%; 58.0%), and had endometrioid histology (83.5%; 67.3%). Favorable stabilized inverse probability of treatment-weighted response profiles were observed for lenvatinib+pembrolizumab versus chemotherapy, including objective response rate (41.6% vs 28.2%), and median times (95% confidence interval) for progression-free survival (13.1 [9.0 to 15.4] vs 8.4 [5.8 to 11.1] months) and overall survival (19.6 [16.9 to 26.3] vs 13.5 [11.9 to 17.6] months). Odds ratios/hazard ratios (95% confidence interval) for objective response rate (odds ratio 2.4 [1.3 to 4.4], p =.005) and progression-free survival (hazard ratio 0.6 [0.4 to 0.9], p <.001) were statistically significant, but not for overall survival (hazard ratio 0.7 [0.4 to 1.0], p =.083). Multi-variable Cox regression findings were consistent with the stabilized inverse probability of treatment weighting analysis.

CONCLUSIONS: Significant clinical benefit of lenvatinib+pembrolizumab in the second-line or later vs single-agent chemotherapy was observed, confirming the Study-309/KEYNOTE-775 findings for use as later-line standard of care in patients with non-microsatellite instability-high/mismatch repair proficient advanced endometrial cancer.