Cancers · Sep 22, 2026

Treatment-Free Interval as a Prognostic Factor for Survival Outcomes in Patients with Advanced or Recurrent Endometrial Cancer Treated with Pembrolizumab Plus Lenvatinib: A Multi-Institutional Real-World Cohort Study

By Su CW, Wang SJ, Shih YH et al.

Background/Objectives: The treatment-free interval (TFI) predicts benefit from platinum rechallenge in gynecological cancers, but its prognostic value in patients receiving second-line pembrolizumab plus lenvatinib for recurrent endometrial cancer (EC) is unknown. We evaluated whether the TFI is associated with survival and toxicity in this setting. Methods: Using the TriNetX Research Network (122 healthcare organizations, United States and Europe), we identified adults aged 18-90 years with advanced or recurrent EC between January 2018 and June 2026 who received three to six cycles of first-line carboplatin plus paclitaxel, progressed, and then received pembrolizumab plus lenvatinib. Patients were stratified by TFI (<6 months, Cohort 1; ≥6 months, Cohort 2) and matched 1:1 by propensity score. The primary outcome was overall survival (OS), compared using Kaplan-Meier and Cox proportional-hazards methods; adverse-event risks were exploratory outcomes compared using z-tests for the risk difference, without adjustment for multiple comparisons. Results: Of 420 eligible patients, 119 remained in each cohort after matching, with balanced baseline characteristics. Median OS was 10.0 months in Cohort 1 versus 23.6 months in Cohort 2 (hazard ratio 1.60, 95% confidence interval 1.12-2.29; p = 0.009), and 3-year OS was 32.5% versus 40.5%. Grade 3 anemia occurred earlier and more often in Cohort 1 (hazard ratio 1.74, 95% confidence interval 1.10-2.76; p = 0.017), whereas hypothyroidism was less frequent (31.9% versus 47.1%; p = 0.017); the remaining adverse events did not differ significantly between cohorts. Conclusions: A TFI ≥ 6 months is associated with significantly longer OS and a largely similar toxicity profile. The TFI is a readily available, real-world evidence-based reference for the prognosis and for the comparative adverse-event profile of the two TFI groups in this setting.

doi.org/10.3390/cancers18193076 Open access PubMed 42882771 Populations