Abstract 5192: Efficacy and safety of second-line therapy by S-1 combined with Sintilimab and Anlotinib in pancreatic cancer patients with liver metastasis: A single-arm, phase II clinical trial

Abstract Background: The mortality of pancreatic cancer is increasing year by year, and the prognosis of pancreatic cancer with liver metastasis is worse. There is still no recognized effective second-line treatment strategy. In this trial, the efficacy and safety of the triple-drug regimen by S-1 chemotherapy combined with anti-PD-1 McAb (Sintilimab) and anti-angiogenic drug (Anlotinib) were evaluated in pancreatic cancer patients with liver metastasis. Methods: Pancreatic cancer patients with liver metastases and ECOG 0~2 were recruited. These patients had never been given 5-FU, anti-PD-1 McAb and/or anti-angiogenic drugs in first-line treatment. S-1 was administered orally at 25 mg/m2 bid from day 1 to day 14, Sintilimab was administered intravenously at 200 mg on day 1, and Anlotinib was administered orally 12mg qd from day 1 to day 14. This method were repeated every 21 days till disease progression. The therapeutic effect was evaluated every 3 cycles. Progression-free survival (PFS) and overall survival (OS) were estimated via the K-M method. Some patients’ tumor tissues have done high-throughput sequencing and the relationship between with effect has been analyzed. Results: From March 2020 to June 2021, a total of 23 patients were enrolled in this study and 19 patients had objective efficacy evaluation. Two patient (10.5%) had confirmed partial response and eight patients (42.1%) had stable disease. Median PFS and OS were 3.53 months and 7.15 months. Grade 3 adverse events were 26.3%, and there were no grade 4 or above adverse events. The tumor tissues of 16 patients have done high-throughput sequencing, and genetic test results show that 6 patients were evaluated as HRD-High and 10 patients as HRD-Low. Patients with HRD-H had shorter PFS than those with HRD-L (2.43 vs. 5.45 months; p = 0.043), However, OS was not significantly different between these two groups (4.43vs.9.35 months; P = 0.11). Conclusions: This study suggests that S-1 chemotherapy combined with anti-PD-1 McAb (Sintilimab) and anti-angiogenic drug (Anlotinib) is efficacy and safety as a second-line treatment for pancreatic cancer patients with liver metastasis. Subgroup analysis showed that patients with HRD-L had longer PFS. HRD-H were found to be related to worsen PFS, which may indicate that other therapies should be explored regarding to these patients. Citation Format: Juan Du, Xin Qiu, Changchang Lu, Huizi Sha, Yahui Zhu, Weiwei Kong, Xing Li, Xiaoping Qian, Baorui Liu. Efficacy and safety of second-line therapy by S-1 combined with Sintilimab and Anlotinib in pancreatic cancer patients with liver metastasis: A single-arm, phase II clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5192.