Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignant melanoma. This study examined the real-world efficacy of dacarbazine in patients who had previously received pembrolizumab, based on the hypothesis that prior ICI treatment enhances the therapeutic response to subsequent chemotherapy.
Methods: This retrospective study included 71 patients with histologically confirmed malignant melanoma treated at Kyungpook National University Chilgok Hospital (Daegu, Korea) between 2011 and 2023. The patients received dacarbazine for unresectable stage IIIC, IIID, or IV melanoma (American Joint Committee on Cancer, 8th edition).
Results: Among the 71 patients, the median patient age was 64 years (range, 25-89 years). When categorized by melanoma subtype, 18 patients (25.4%) had acral melanoma, 40 (56.3%) had cutaneous melanoma, and 13 (18.3%) had mucosal melanoma. Sixteen of the dacarbazine-treated patients had not received pembrolizumab previously (DTI-only group), while 55 had (pem-DTI group). The median progression-free survival was 2.3 months in the DTI-only group and 3.9 months in the pem-DTI group (hazard ratio [HR], 0.246; 95% confidence interval [CI], 0.106-0.576; p=0.001). The median overall survival was 6.8 months in the DTI-only group and 19.0 months in the pem-DTI group (HR, 0.198; 95% CI, 0.068-0.574; p=0.003). The duration of response (DoR) was 4.64 months in the DTI group and 8.11 months in the pem-DTI group.
Conclusion: This study demonstrated that the DoR to dacarbazine was prolonged following ICI therapy (4.64 months vs. 8.11 months). This indicates that prior ICI treatment may enhance tumor sensitivity to chemotherapy, making dacarbazine a viable option for treating refractory, relapsed, or progressive melanoma.
Keywords: Dacarbazine; Immune-check point inhibitors; Melanoma; Tumor microenvironment.