INTRODUCTION
Melanoma is the leading cause of skin cancer-related mortality worldwide.¹ Advances in anti-programmed cell death protein 1 (PD-1) therapies, such as pembrolizumab, have significantly improved survival outcomes in advanced melanoma.² However, the optimal duration of pembrolizumab treatment remains uncertain and real-world treatment durations vary.³
Pembrolizumab, administered via outpatient infusion every 3 or 6 weeks, has demonstrated significantly reduced mortality compared with standard chemotherapy in advanced melanoma.2,3 The KEYNOTE trials, including KEYNOTE-001 and KEYNOTE-006, were designed to assess the safety and efficacy of pembrolizumab.2,3 These trials relied on physician-determined clinical responses to guide treatment discontinuation rather than a predefined treatment duration.4 Although the median treatment duration in the KEYNOTE-001 trial was approximately 5.6 months, a subset of patients continued pembrolizumab therapy safely beyond 12 months, with durable clinical responses.2,3 Similarly, the KEYNOTE-006 trial allowed treatment for up to 24 months, and some patients who completed the full course achieved long-term disease control.5 However, these trials did not directly compare different pembrolizumab treatment durations, leaving unanswered the question of whether prolonged therapy provides further survival advantages.5
To address this gap, we conducted a large, retrospective cohort study using the TriNetX research network to evaluate the impact of pembrolizumab duration on overall mortality in stage III and stage IV melanoma. Specifically, we aimed to
Pembrolizumab, administered via outpatient infusion every 3 or 6 weeks, has demonstrated significantly reduced mortality compared with standard chemotherapy in advanced melanoma.2,3 The KEYNOTE trials, including KEYNOTE-001 and KEYNOTE-006, were designed to assess the safety and efficacy of pembrolizumab.2,3 These trials relied on physician-determined clinical responses to guide treatment discontinuation rather than a predefined treatment duration.4 Although the median treatment duration in the KEYNOTE-001 trial was approximately 5.6 months, a subset of patients continued pembrolizumab therapy safely beyond 12 months, with durable clinical responses.2,3 Similarly, the KEYNOTE-006 trial allowed treatment for up to 24 months, and some patients who completed the full course achieved long-term disease control.5 However, these trials did not directly compare different pembrolizumab treatment durations, leaving unanswered the question of whether prolonged therapy provides further survival advantages.5
To address this gap, we conducted a large, retrospective cohort study using the TriNetX research network to evaluate the impact of pembrolizumab duration on overall mortality in stage III and stage IV melanoma. Specifically, we aimed to
