Introduction/Background The adjuvant treatment of endometrial carcinoma is constantly evolving. The introduction of checkpoint inhibitors in the therapy of recurrent endometrial carcinoma marked a milestone in the clinical outcome. Nevertheless, there is a need to develop possible treatment strategies to overcome a checkpoint inhibitor resistance.

Results We present a case of 79-year-old patient diagnosed with endometrioid endometrial carcinoma in 2010. Laparoscopically assisted vaginal hysterectomy with salpingo-oophorectomy and systematic pelvic and paraaortic lymphadenectomy was performed, and the carcinoma was classified as pT1b G2 R0 L0 V0 FIGO IB. Two years later a vaginal stump recurrence was resected, macroscopically tumor free. Five years after initial diagnosis, the patient presented with pulmonary metastasis. Chemotherapy was started with weekly paclitaxel and carboplatin for twelve cycles. Moreover, the patient underwent combined radio-chemotherapy in June 2016. Six months later the patient was first diagnosed with cerebral metastasis, stereotactic radiation was followed by MPA for 10 months. In November 2017 due to the third local recurrence, a laparotomy with resection of the tumor from the pelvic wall and the iliac vessels was performed and letrozol therapy was initiated until January 2020. A pathological examination confirmed an EEC – p53 wt, hormone receptor positive and a microsatellite instability with loss of PMS2 and MLH1. In 2020 the patient presented infiltration of the bladder. Immunotherapy with checkpoint inhibitor was initiated but the tumor showed image morphological progression after 9 months. Due to the progression the addition of lenvatinib was recommended. Under this combination therapy the tumor showed a stable disease ever since in total of 21 months and with some lesions to partial response.

Conclusion The combination of checkpoint inhibitor and a tyrosine kinase inhibitor is a potential approach to overcome checkpoint inhibitor resistance. Further clinical trials are warranted.