Modern Approach to Melanoma Adjuvant Treatment with Anti-PD1 Immune Check Point Inhibitors or BRAF/MEK Targeted Therapy: Multicenter Real-World Report

Abstract

Background: The landscape of melanoma management changed as randomized trials have launched adjuvant treatment. Materials and Methods: An analysis of data on 248 consecutive melanoma stage III and IV patients given adjuvant therapy in eight centers (February 2019 to January 2021) was conducted. Results: The analyzed cohort comprised 147 melanoma patients given anti-PD1 (33% nivolumab, 26% pembrolizumab), and 101 (41%) were given dabrafenib plus trametinib (DT). The 2-year overall survival (OS), relapse-free survival (RFS), and distant-metastases-free survival (DMFS) rates were 86.7%, 61.4%, and 70.2%, respectively. The disease stage affected only the RFS rate; for stage IV, it was 52.2% (95% CI: 33.4–81.5%) vs. 62.5% (95% CI: 52.3–74.8%) for IIIA-D, p = 0.0033. The type of lymph node surgery before adjuvant therapy did not influence the outcomes. Completion of lymph node dissection cessation after positive SLNB did not affect the results in terms of RFS or OS. Treatment-related adverse events (TRAE) were associated with longer 24-month RFS, with a rate of 68.7% (55.5–84.9%) for TRAE vs. 56.6% (45.8–70%) without TRAE, p = 0.0031. For TRAE of grade ≥ 3, a significant decline in OS to 60.6% (26.9–100%; p = 0.004) was observed. Conclusions: Melanoma adjuvant therapy with anti-PD1 or DT outside clinical trials appears to be effective and comparable with the results of registration studies. Our data support a de-escalating surgery approach in melanoma treatment.

Deciphering the role of adjuvant therapy in melanoma and its actual benefits

“…This disparity persisted in both the overall group and the BRAF/+/group (Figure 5). 27 BRAF/+/melanoma patients exhibited higher 2‐year RFS rates in the entire cohort and the BRAF/MEK inhibitor‐treated group compared to those treated with anti‐PD‐1 antibodies. The impact of treatment‐related adverse events on OS and RFS was consistent across subpopulations defined by surgery prior to adjuvant treatment.…”

“…A retrospective analysis of 82 cases of nivolumab, 65 cases of pembrolizumab, and 101 cases of BRAF/MEK inhibitors indicated a significantly longer RFS in the BRAF/MEK inhibitor group with no significant difference in OS. The 2‐year OS, RFS, and DMFS rates were 86.7%, 61.4%, and 70.2%, respectively 27 . Lymph node surgery before adjuvant therapy and the type of drug used did not significantly influence 2‐year OS for the entire group ( p = 0.6318) (Figure 4a).…”

“…Lymph node surgery before adjuvant therapy and the type of drug used did not significantly influence 2‐year OS for the entire group ( p = 0.6318) (Figure 4a). 27 However, there was a notably unfavorable difference in RFS rates for anti‐PD‐1 adjuvant treatment, especially early in the observation period (Figure 4b). This disparity persisted in both the overall group and the BRAF/+/group (Figure 5).…”

“…Placzke et al. present real‐world evidence on the use of anti‐PD‐1 antibodies and BRAF/MEK inhibitors for postoperative adjuvant melanoma in eight Polish centers 27 . A retrospective analysis of 82 cases of nivolumab, 65 cases of pembrolizumab, and 101 cases of BRAF/MEK inhibitors indicated a significantly longer RFS in the BRAF/MEK inhibitor group with no significant difference in OS.…”

“…(a) Overall and (b) relapse‐free survival in relation to the type of drugs used; BRAF/MEK inhibitors versus anti‐PD‐1 antibodies. Adopted from Placzke et al 27 …”