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

• Published in: Journal for immunotherapy of cancer 2022-02, Vol.10 (2), p.e004036
• Main Authors: Li, Siming, Wu, Xiaowen, Yan, Xieqiao, Zhou, Li, Chi, Zhihong, Si, Lu, Cui, Chuanliang, Tang, Bixia, Mao, Lili, Lian, Bin, Wang, Xuan, Bai, Xue, Dai, Jie, Kong, Yan, Tang, Xiongwen, Feng, Hui, Yao, Sheng, Flaherty, Keith T, Guo, Jun, Sheng, Xinan
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antibodies; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Axitinib - pharmacology; Axitinib - therapeutic use; Biomarkers; Biomarkers, Tumor - metabolism; Biopsy; Cancer; Chemotherapy; Clinical/Translational Cancer Immunotherapy; combination; Disease; Drug dosages; drug therapy; Female; Gene expression; Growth factors; Humans; Immunotherapy; Kinases; Male; Medical prognosis; Melanoma; Melanoma - drug therapy; Melanoma - mortality; Melanoma - pathology; Metastasis; Mutation; Patients; Prospective Studies; Response rates; Software; Survival Analysis; Targeted cancer therapy; Time Factors; tumor; White people
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2021-004036

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.