Efficacy and safety of anlotinib plus anti‑PD‑1 agents in patients with refractory advanced biliary tract cancers

• Tianqi An ^[1] ; Hong Zong ^[1] ; Shuang Hu ^[1] ; Yiyi Liu ^[1] ; Ruihua Zhao ^[1] ; Qiu Hu ^[2] ; Linhua Liu ^[3] ; Xinguang Cao ^[4] ; Rui Li ^[5] ; Jia Li ^[6]
  1. [1] Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  2. [2] Department of HPB Surgery, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China
  3. [3] Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
  4. [4] Department of Digestive Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  5. [5] Department of Respiratory Intervention, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
  6. [6] Department of Integrated Chinese and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 8, 2024, págs. 2006-2019
• Idioma: inglés
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• Resumen

  • Background Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs).

    Methods A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers.

    Results Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35–11.45) and 13.9 months (95% CI: 5.39–22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17–5.03) and 13.2 months (95% CI: 8.72–17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 μg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008).

    Conclusions The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluo- ropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.