Cross-sectional study of long-term Health-Related Quality of Life in stage III melanoma patients receiving neo-adjuvant versus adjuvant immune checkpoint inhibitors

Background: Neoadjuvant (PD-1 and PD-1+ CTLA-4 blockade) immune checkpoint inhibitors (ICI) have been shown to induce high response rates and to be superior as compared to adjuvant standard of care (PD-1 blockade) in stage III melanoma patients. While higher grade 3/4 toxicity of neoadjuvant therapy does not appear to impact early Health-Related Quality of Life (HRQoL), long-term data are missing. Purpose: A single-center, cross-sectional analysis comparing late HRQoL outcomes of stage III melanoma patients two years after therapy initiation receiving either neoadjuvant or adjuvant ICI therapy. Methods: Patients who received either neoadjuvant ICI or adjuvant ICI between 2019 and 2020 were included. Long-term HRQoL was assessed two years after start of therapy (median 2.5 years (IQR = 2.3–2.6)) using the EORTC QLQ-C30 questionnaire. Defined clinically relevant thresholds for HRQoL impairment were used to compare the two treatment groups. Multivariable linear and logistic regression analyses were performed to estimate whether neoadjuvant ICI therapy was independently associated with HRQoL outcomes. Results: Patients treated with neoadjuvant ICI (n = 42) reported significantly better long-term HRQoL scores compared to patients treated with adjuvant ICI (n = 60): physical (93 vs 88; P = 0.020), role (93 vs 84; P = 0.018), cognitive (86 vs 77; P = 0.033), and social functioning (92 vs 85; P = 0.046), and less fatigue (13 vs 23; P = 0.012). Multivariable regression analysis showed that neoadjuvant ICI (vs. adjuvant ICI) was independently associated with less fatigue. Conclusion: Patients treated with neoadjuvant ICI reported a clinically relevant and superior long-term HRQoL two years after treatment initiation compared to patients treated with adjuvant ICI. These findings support that neoadjuvant ICI therapy should be considered for implementation into standard clinical practice.