Axitinib Plus Anti-PD1 Regimen Is Effective as First-line Mucosal Melanoma Treatment

A retrospective study on the combination of a vascular endothelial growth factor receptor inhibitor plus programmed cell death-1 blockade added to evidence of efficacy in early trials.

The combination of a vascular endothelial growth factor receptor (VEGFR) inhibitor and programmed cell death-1 (PD-1) antibody has shown effectiveness in early trials for advanced mucosal melanoma, an aggressive subtype with oncogenic drivers distinct to those in cutaneous melanoma. A retrospective study published in the European Journal of Cancer aimed to evaluate the efficacy and safety of the treatment in the real-world setting.

A total of 81 patients with advanced mucosal melanoma treated with axitinib plus anti–PD-1 antibody as first-line therapy and 66 patients treated with the regimen as salvage therapy were included in the study. Patients were identified at the Peking University Cancer Hospital and Institute in China between August 2018 and May 2020.

Treatment included 5 mg of oral axitinib twice per day and either anti–PD-1 antibody toripalimab (3 mg/kg intravenously every 2 weeks) or pembrolizumab (2 mg/kg intravenously every 3 weeks). Tumor responses were assessed every 8 weeks with CT scans or MRI and based on the Response Evaluation Criteria in Solid Tumors version 1.1.

The primary endpoint of the study was overall response rate (ORR), including complete response (CR) or partial response (PR). Disease control rate (DCR), duration of response (DOR), time to treatment failure (TTF), overall survival (OS), and treatment-related adverse events (TRAEs) were secondary endpoints.

The most common site of disease was the sinonasal cavity (32.7%), followed by anorectum, genitourinary tract, esophagus, oral cavity, and conjunctivum. In the first-line cohort, 16% of patients had liver metastasis, compared with 45.5% in the salvage therapy cohort. Of the patients with liver metastasis, 53.5% underwent transcatheter arterial chemoembolization (TACE) as additional local therapy.

The median follow-up from the start of axitinib plus anti–PD-1 antibody was 20.1 months, and ORR in the overall cohort was 24.5% (95% CI, 17.3-31.6) with no statistical difference between primary sites of disease. In the first-line setting, ORR was 30% (95% CI, 19.7-40.3) versus 17.5% (95% CI, 7.8-27.1) as salvage therapy.

In patients with liver metastasis, ORR was 26.1% (95% CI, 6.7-45.5) in those who underwent TACE and 15% (95% CI, 2.1-32.1) in those who did not undergo TACE.

DCR on the combination regimen was 72.7% (95% CI, 65.3-80.1). The median TTF was 5.2 months (95% CI, 3.7-6.6), DOR was 9.2 months (95% CI, 7.2-11.2), and OS was 11.1 months (95% CI, 7.2-15.0).

Sex, age, primary anatomic sites, disease stage, liver metastasis, and brain metastasis were not strong prognostic factors, and nor was the type of anti–PD-1 therapy. Poor Eastern Cooperative Oncology Group status and elevated LDH, however, may predict shorter TTF and OS.

The authors noted that while this is the largest analysis of anti–PD-1 therapy plus anti-VEGFR inhibitors in advanced mucosal melanoma to date that they know of, limitations include the study’s retrospective design and the lack of PD-L1 expression testing, which might have been predictive of response to the treatment.


Tang B, Mo J, Yan X, et al. Real-world efficacy and safety of axitinib in combination with anti-programmed cell death-1 antibody for advanced mucosal melanoma. Eur J Cancer. Published online August 20, 2021. doi:10.1016/j.ejca.2021.07.018

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