Second and subsequent lines of systemic therapy in endometrial cancer - a real-life clinical experience

Patients with advanced or recurrent endometrial cancer who progress after platinum-based chemotherapy face a poor prognosis, and treatment options have historically been limited. The introduction of immunotherapy, alone or in combination with targeted agents, has substantially expanded therapeutic options in subsequent treatment lines. This study evaluated the efficacy and clinical benefit of second- and subsequent-lines of systemic therapy in a real-life cohort of patients with advanced or recurrent endometrial cancer.

This retrospective, single-center analysis included patients treated at University Hospital Brno who were considered for second-line systemic therapy after failure of platinum-based chemotherapy between 2013 and 2024. Clinicopathological and molecular characteristics, systemic treatment modalities, best overall response, time to progression, and disease-specific survival were assessed.

A total of 43 patients were identified; second-line treatment was initiated in 41 patients (95.3%). Of these, 26 (63.4%) received second-line chemotherapy, 14 (34.1%) received pembrolizumab alone or in combination with lenvatinib, and one patient (2.4%) received hormonal therapy. The median disease-specific survival for the entire cohort was 13.4 months (95% confidence interval 8.5-27.2 months). Among patients with re-administration of platinum-based chemotherapy, the median disease-specific survival was 27.2 months. Patients receiving pembrolizumab ± lenvatinib had a median survival of 23.4 months, whereas those treated with non-platinum chemotherapy had a median survival of 6.7 months. Two patients without active second-line treatment had a median disease-specific survival of 2.7 months. Nearly half of the patients treated with pembrolizumab ± lenvatinib experienced a prolonged time to progression compared with those receiving primary platinum-based chemotherapy.

In patients with advanced or recurrent endometrial cancer after platinum failure, active systemic therapy may prolong survival and improve disease control. The greatest clinical benefit was observed with pembrolizumab alone or in combination with lenvatinib. An individualized, sequential approach to palliative systemic therapy is crucial to maximize clinical benefits.