Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis

• DOI: 10.1136/jitc-2021-004036
• Publication Date: 2022-02-22T16:25:49Z
• Authors: Siming Li; Xiaowen Wu; Xieqiao Yan; Li Zhou; Zhihong Chi; Lu Si; Chuanliang Cui; Bixia Tang; Lili Mao; Bin Lian; Xuan Wang; Xue Bai; Jie Dai; Yan Kong; Xiongwen Tang; Hui Feng; Sheng Yao; Keith T Flaherty; Jun Guo; Xinan Sheng
• Keywords: Male; Time Factors; Axitinib; Immunobiology of Dendritic Cells; Immunology; Chimeric Antigen Receptor T Cell Therapy; Cancer research; Antibodies, Monoclonal, Humanized; Biochemistry; Cancer Immunotherapy; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Health Sciences; Biomarkers, Tumor; Sunitinib; Humans; Prospective Studies; Melanoma; Internal medicine; RC254-282; Cancer; Clinical/Translational Cancer Immunotherapy; Immunology and Microbiology; FOS: Clinical medicine; Gastroenterology; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Life Sciences; Biomarker; Survival Analysis; Tumor Regression; 3. Good health; Chemistry; Oncology; Medicine; Female

BackgroundMucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a phase Ib study. Here, we report the updated overall survival (OS), duration of response (DoR), and biomarker analysis results.MethodsPatients with advanced MM received toripalimab 1 or 3 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally two times per day until disease progression or unacceptable toxicity. Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) by messenger RNA sequencing were evaluated for correlation with survival.ResultsAs of April 2, 2021, the median follow-up was 42.5 months. Among 29 chemotherapy-naïve patients with metastatic MM, the median OS was 20.7 months (95% CI 9.7 to 32.7 months); the median progression-free survival (PFS) was 7.5 months (95% CI 3.8 to 14.8 months); and the median DoR was 13.4 months (95% CI 5.5 to 20.6 months). The OS rates of 1, 2, and 3 years were 62.1%, 44.8%, and 31.0%, respectively. Biomarker analysis found that PD-L1 expression and TMB level were not associated with survival benefits. In contrast, a 12-GEP signature correlated with improved PFS (17.7 vs 5.7 months, p=0.0083) and OS (35.6 vs 17.6 months, p=0.039).ConclusionsThe 3-year survival update confirmed the antitumor activity and long-term survival benefit of the toripalimab plus axitinib combination in patients with advanced MM. The 12-gene GEP is of value in predicting the outcomes of vascular endothelial growth factor receptor-tyrosine kinase inhibitor and PD-1 blockade combination therapy, but requires further validation.Trial registration numbersNCT03086174.