# Extended therapeutic efficacy of dacarbazine following prior treatment with immune checkpoint inhibitors in metastatic melanoma: a single center retrospective study in Korea

## TL;DR

This study found that dacarbazine chemotherapy was more effective in melanoma patients who previously received pembrolizumab, suggesting prior immunotherapy may improve chemotherapy outcomes.

## Contribution

The study shows for the first time in a real-world setting that prior ICI treatment enhances dacarbazine efficacy in metastatic melanoma.

## Key findings

- Patients who received pembrolizumab before dacarbazine had longer progression-free and overall survival.
- Duration of response to dacarbazine was significantly prolonged in patients with prior ICI treatment.
- Prior ICI therapy may increase tumor sensitivity to chemotherapy in refractory melanoma.

## Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignant melanoma. This study examined the real-world efficacy of dacarbazine (dimethyl triazeno imidazole carboxamide, DTIC) in patients who had previously received pembrolizumab, based on the hypothesis that prior ICI treatment enhances the therapeutic response to subsequent chemotherapy.

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 DTIC for unresectable stage IIIC, IIID, or IV melanoma (American Joint Committee on Cancer, 8th edition).

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 DTIC-treated patients had not received pembrolizumab previously (DTIC-only group), while 55 had (pem-DTIC group). The median progression-free survival was 2.3 months in the DTIC-only group and 3.9 months in the pem-DTIC 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 DTIC-only group and 19.0 months in the pem-DTIC group (HR, 0.198; 95% CI, 0.068–0.574; p=0.003). The duration of response (DoR) was 4.64 months in the DTIC group and 8.11 months in the pem-DTIC group.

This study demonstrated that the DoR to DTIC 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 DTIC a viable option for treating refractory, relapsed, or progressive melanoma.