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Longer Pembrolizumab Therapy Reduces Mortality in Stage III and IV Melanoma: A TriNetX Study
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.
