LAUSR

e17124 Background: The immunotherapy drug, nivolumab, is now approved for several metastatic cancers, and has resulted in responses previously not seen with these cancers. Molecular targeting agents, such as mammalian target of rapamycin (mTOR) inhibitor, have also recently been shown to have modest activity for endometrial cancers, however, the efficacy was limited.　The present retrospective analysis is to evaluate the efficacy of Nivolumab alone or combination with molecular targeting agents for recurrent and refractory endometrial cancers. Methods: A retrospective evaluation for medical charts of the patients were conducted: (a) the cases with histologically confirmed endometrial cancers, (b) those that had recurrent diseases, (c) diagnosed as refractory for the previous chemotherapy, (d) those that were treated with combination therapy using tri-weekly Nivolumab (100mg/body, every 3 weeks) alone, or combination with molecular targeting agents. The association with serum markers and response was also investigated. Results: A total of 16 patients were identified: 5 cases with endometrioid G1/2, 4 cases with endometrioid G3, and the 6 cases with serous, and one case with mucinous histology. Median age was 61 years old (range:43-76), and median number of the previous chemotherapy was 4 regimens (range:1-5). Combined drugs included everolimus (n = 9), temozolomide (n = 1), trametinib (n = 1), and nintedanib (n = 1). Among 12 cases with evaluable disease, a complete response over 20 months was observed in one case: a case with endometrial carcinoma G2 treated with Nivolumab and evelorimus (5mg/day, continuously). Stable disease more than three months was achieved in 8 cases (67%), and clinical benefit rate (CR+SD > 3months) was achieved in 75% of the cases. Median progression-free survival was 5 months (range: 3-20+). Non-hematological adverse events included general fatigue, mucositis, dysgeusia, skin rash, edema, and liver dysfunction, but the toxicity greater than grade2 was observed and in a case with liver dysfunction (G3). There was no significant relationship between response and serum levels of VEGF, p53, and IL-6, however, clinical benefit was observed in higher abundance of endometrioid histology compared with serous subtype (86% vs. 50%). Conclusions: Combination therapy using Nivolumab with evelolimus could be a candidate for recurrent and refractory endometrial cancers. Biomarker analyses for the responders are mandatory for further investigation for larger clinical studies.