Temozolomide Reconsidered: Real-World Evidence in Resistant Melanoma Cases

Abstract Immune checkpoint inhibitors have transformed outcomes in melanoma and other aggressive malignancies. However, subsequent lines of therapy remain limited: modest efficacy, lack of publicly funded options, and declining performance status frequently restrict clinicians’ choices. In this context, temozolomide has re-emerged as a feasible bridge therapy, with emerging evidence suggesting synergistic activity when used alongside anti–PD-1 agents. Here, we describe two cases of single-agent temozolomide administered after progression on prior systemic therapies, including anti–PD-1 and, in one case, targeted therapy, both demonstrating meaningful clinical responses and great patient tolerability. We also briefly discuss how these observations may support further exploration of temozolomide within modern treatment sequencing strategies.