BACKGROUND: Melanoma is the leading cause of skin-cancer-related mortality worldwide. Anti-programmed cell death protein-1 therapies, including pembrolizumab, play a critical role in treating advanced melanoma. However, the optimal treatment duration remains undetermined. OBJECTIVE: To evaluate whether longer durations of pembrolizumab therapy improve overall mortality in stage III and stage IV melanoma. METHODS: We conducted a retrospective cohort study using the TriNetX platform, including 234 patients who received 24+ months of therapy (long-term) and 796 patients who received 12 to 24 months (intermediate-duration). A cohort of 746 patients who received pembrolizumab for 7 to 10 months (short-term) served as the comparison group. Mortality, hospitalizations, serum lactate dehydrogenase (LDH) levels, and adverse events were analyzed over 10 years using Cox proportional hazards regression with propensity score matching. RESULTS: Long-term therapy significantly reduced overall mortality (HR = 0.41, 95% CI: 0.27-0.62) compared with short-term therapy. Intermediate-duration therapy also reduced mortality (HR = 0.47, 95% CI: 0.37-0.60) and hospitalizations (HR = 0.74, 95% CI: 0.68-0.93). Differences in LDH levels and adverse events did not reach statistical significance. CONCLUSIONS: Longer durations of pembrolizumab therapy reduces overall mortality in stage III and stage IV melanoma, reinforcing its safety and utility. Prospective studies are needed to confirm these findings.
Gipple et al. (Wed,) studied this question.