Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
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Siming Li1, Xiaowen Wu1, Xieqiao Yan1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Background:
Mucosal 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.
Methods:
Patients 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.
Results:
As 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).
Conclusions:
The 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 Numbers:
NCT03086174.
Insights
The combination of toripalimab (anti-PD-1) and axitinib shows long-term survival benefits for metastatic mucosal melanoma. A 12-gene signature predicts patient outcomes, unlike PD-L1 or TMB levels.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Mucosal melanoma is an aggressive cancer with limited treatment options.
- Standard anti-PD-1 therapy shows poor response rates in mucosal melanoma patients.
Purpose of the Study:
- To report updated overall survival (OS), duration of response (DoR), and biomarker analysis from a phase Ib study.
- To evaluate the efficacy of combining toripalimab with axitinib in metastatic mucosal melanoma.
Main Methods:
- Patients received toripalimab (anti-PD-1) plus axitinib until disease progression or toxicity.
- Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) were analyzed.
Main Results:
- Median OS was 20.7 months, median PFS was 7.5 months, and median DoR was 13.4 months.
- 3-year OS rate was 31.0%.
- A 12-gene GEP signature correlated with improved PFS and OS, while PD-L1 and TMB did not.
Conclusions:
- The combination of toripalimab and axitinib demonstrates sustained antitumor activity and long-term survival benefits.
- A 12-gene GEP signature may predict treatment outcomes for this combination therapy, warranting further validation.
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