The combination of the multitargeted tyrosine kinase inhibitor lenvatinib and the anti-PD-1 monoclonal antibody pembrolizumab improved survival versus chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.1 The ENGOT-en9/LEAP-001 study evaluated the role of this combination in the first-line setting.2
METHODS
The global, open-label, phase III ENGOT-en9/LEAP-001 study randomised 842 patients with stage III-IV or recurrent endometrial cancer to receive (1:1) lenvatinib plus pembrolizumab or paclitaxel plus carboplatin. Included patients received no prior chemotherapy or had disease progression ≥6 months after (neo)adjuvant platinum-based chemotherapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), evaluated in the mismatch repair-proficient (pMMR) and all-comers population.
RESULTS
A total of 642 patients had pMMR tumours and 200 patients had mismatch repair-deficient (dMMR) tumours. At the final analysis, after a median follow-up of 38.4 months, median PFS in the pMMR population was 9.6 months with lenvatinib plus pembrolizumab compared to 10.2 months with chemotherapy (HR[95% CI]: 0.99[0.82-1.21]), and among all-comers 12.5 months compared to 10.2 months (HR[95% CI]: 0.91[0.76-1.09]). Median OS in the pMMR population was 30.9 months with lenvatinib plus pembrolizumab versus 29.4 months with chemotherapy (HR[95% CI]: 1.02[0.83-1.26], non-inferiority p= 0.246 – not statistically significant) and among all-comers 37.7 months versus 32.1 months (HR[95% CI]: 0.93[0.77-1.12]). Exploratory subgroup analyses found improved PFS and OS in the subgroup of patients with dMMR tumours, and the subgroup of patients who had received prior (neo)adjuvant chemotherapy in the pMMR and all-comers population. Objective response rate was 51% with lenvatinib plus pembrolizumab versus 55% with chemotherapy in the pMMR population, and 56% versus 55%, respectively, in the all-comers population. Grade ≥3 treatment-related adverse events occurred in 79% versus 67% of patients treated with lenvatinib plus pembrolizumab and chemotherapy, respectively.
CONCLUSIONS
In patients with recurrent or advanced endometrial cancer, first-line treatment with lenvatinib plus pembrolizumab did not improve PFS or OS compared to chemotherapy, either in all-comers or patients with pMMR disease.
References
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