Comparative analysis of adjuvant therapy for stage III BRAF‐mut melanoma: A real‐world retrospective study from single center in China

Abstract

Background BRAF V600 mutation is the most common oncogenic alternation in melanoma and is visible in around 50% of cutaneous and 10%–15% of acral or mucosal subtypes. Currently, immunotherapy with anti‐PD‐1 blockade and dual‐targeted therapy with Dabrafenib plus trametinib (D + T) target therapy have been approved as adjuvant therapies for Stage III melanoma with BRAF V600 mutation. According to their phase III clinical trials, 3‐year recurrence‐free survival (RFS) is around 60% for both types of treatment. However, early disease control was slightly more effective with targeted therapy than immunotherapy. With different drug approval deadlines in China, anti‐PD1 monotherapy, D + T combination, and Vemurafenib (V) monotherapy have all been used in real clinical practice as adjuvant settings for stage III BRAF‐mut melanoma in recent years. We conducted this retrospective study to evaluate the efficacy of different treatments in the Chinese melanoma population. Methods Patients who underwent radical surgery and were diagnosed as Stage III melanoma harboring BRAF V600 mutation by pathological report were retrospectively identified at Fudan University Shanghai Cancer Center from January 2017 to December 2021. Patients with mucosal melanoma, or with follow‐up of <6 months, or receiving other adjuvant treatment were excluded. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different adjuvant groups. Log‐rank analysis was used to identify prognostic factors for relapse‐free survival (RFS). Results Ninety‐three patients with resected stage III melanoma with BRAF V600E mutation were identified in our study, including 25 patients receiving adjuvant anti‐PD‐1 immunotherapy (PD‐1), 25 receiving adjuvant D + T, 23 receiving V, and 20 patients with observation‐only (OBS). There were no statistical differences between treatment groups in baseline characteristics including age, gender, subtypes, primary thickness, ulceration, and nodal involvement. Median relapse‐free survival (RFS) time was not reached in the D + T group, 15 months in the V group, 15 months in the PD‐1 group, and 10 months in the OBS group, respectively. Compared to OBS, all three other groups showed a tendency to benefit from RFS, while only D + T achieved a statistical difference (p = 0.002). However, compared to D + T, anti‐PD‐1 monotherapy also showed significantly worse relapse control (p = 0.032). Conclusions For Chinese stage III melanoma with BRAF mutation, both novel targeted therapy and immunotherapy showed potential benefits in relapse‐free survival compared to observation only. Dual‐targeted D + T therapy may still be the best choice for adjuvant therapy because anti‐PD‐1 monotherapy has failed to report equivalent efficacy in real‐world practice.

Prognostic Value of the Width of Invasion in pT3 Cutaneous Melanomas

“…At present, patients with pT3 cutaneous melanomas and lymph node metastasis (stage IIIB/IIIC) are usually treated with neoadjuvant therapy, which may also include BRAF/MEK inhibitors and immune modulators [50][51][52]. Nevertheless, not all pT3 cases undergo sentinel lymph node biopsy and even among those that do the positivity rate is around 11% [53].…”

The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas

“…Even though complete lymph node dissection does not influence PFS or OS [25], positive SNLB is associated with decreased PFS and OS and should be treated more aggressively [35,36,41]. Since positive SLNB in thick melanomas automatically increases staging from IIB/IIC to IIIC [29], such patients may be treated with adjuvant systemic therapy, including newer drugs such as immune-checkpoint inhibitors and/or BRAF/MEK inhibitors, which have been shown to improve PFS and OS [41,[55][56][57][58][59]. Nevertheless, thick cutaneous melanomas have a poor prognosis even in cases of negative SLNB [34], and adjuvant therapy may be beneficial for all patients with melanomas > 4 mm regardless of SLNB status [60,61].…”