Outcomes of Neoadjuvant Therapy in Advanced Melanoma: A Systematic Review and Meta-Analysis. Publisher



Shahzad M ; Khalid MF ; Kasaeian A ; Khan A ; Khan S ; Noor J ; Khan I ; Oskouie I ; Alemi H ; Warraich SZ ; Anwar I ; Amin MK ; Jaglal MV
Source: Journal of Clinical Oncology Published:2025

Abstract

e21543Background: Neoadjuvant therapy has emerged as a promising approach in the management of melanoma, offering potential advantages over traditional adjuvant therapy. Early immune activation and tumor burden reduction may contribute to these benefits. However, variability in outcomes across studies exist. Here, we performed a systematic review and meta-analysis to further evaluate the efficacy and safety of neoadjuvant versus adjuvant therapy in melanoma treatment. Methods: A systematic search was conducted on PubMed, Cochrane, and Clinicaltrials.gov following PRISMA guidelines and eight studies reporting outcomes of neoadjuvant treatment in melanoma were included after screening of 1318 studies. Inter-study variance was assessed using the Der Simonian-Laird Estimator, and pooled analysis was conducted with 95% confidence intervals using the ‘meta’ package in R (version 4.16-2). Results: A total of 1072 patients (neoadjuvant: 534, adjuvant:538) from 8 studies (2018-2024) were included in the analysis. The median age was 61.6 (19-90) years and 59.9 (19-88) years, respectively. Majority were male (65% vs 70%) and all the patients had stage III/IV melanoma. All studies were phase II/III trials. Median follow up time was 24.3 (2.8-84) months. Most commonly used regimen in intervention group included ipilimumab + nivolumab. When compared between neoadjuvant and adjuvant arms, the pooled median event-free survival (mEFS) was 49.84 vs 26.5 months and EFS rates at 6, 12, 18, and 24 months were 88.4%, 80.3%, 74.1%, and 68.2% vs 71.7%, 59.7%, 52.8%, and 50.9%, respectively. For the neoadjuvant group, the pooled rates of complete response (CR) and partial response (PR) were 47% (95%CI: 27%-68%, I2= 94, p < 0.01, n = 428) and 22% (95%CI: 1%-42%, I2= 94, p < 0.01, n = 381), respectively. The pooled rates of stable disease (SD) and progressive disease (PD) were 19% (95%CI: 5%-34%, I2= 74, p = 0.02, n = 239) and 3% (95%CI: 1%-6%, I2= 6, p = 0.36, n = 297), respectively. The pooled rate of adverse events (AE) was 58.9% (CI 54%-64%, I2= 99, p < 0.01, n = 438) for neoadjuvant therapy. Conclusions: Neoadjuvant therapy significantly improves event-free survival and response rates in high-risk melanoma compared to adjuvant therapy. These findings support neoadjuvant therapy as a promising approach to enhance long-term outcomes. Further research is needed to standardize treatment strategies and optimize patient selection. © 2025 by American Society of Clinical Oncology