Clinical outcomes and safety of adjuvant therapy in patients with high-risk melanoma harboring BRAF V600 mutations: A multicenter, retrospective cohort study.

Abstract

e21565 Background: High-risk melanoma encompasses deep primary tumors, with or without ulceration (stages IIB and IIC), as well as regional lymph node involvement (stage III). BRAF mutations are present in 40% to 60% of melanoma cases. The advent of immunotherapy and BRAF/MEK inhibitors has markedly enhanced the prognosis for patients receiving adjuvant therapy. Nonetheless, there exists a paucity of data directly comparing these therapeutic modalities in the Chinese patient population. Methods: This study included high-risk melanoma patients aged 18 years and older with BRAF V600 mutations who had undergone resection of primary or metastatic lesions. Participants were stratified into four cohorts based on the type of adjuvant therapy received: high-dose interferon(HDI), PD-1 antibody monotherapy, dabrafenib and trametinib (D/T), and a combination of BRAF±MEK inhibitors and PD-1 antibody. The primary endpoints were relapse-free survival (RFS) and distant metastasis-free survival (DMFS). RFS was defined as the interval from the final surgical intervention to local recurrence and/or distant metastasis or death, or the last follow-up, whichever occurred first. DMFS was defined as the time from definitive surgery to the onset of any distant metastasis or death, whichever occurred first. Results: During a median follow-up period of 20 months (IQR: 11–33), significant differences were observed in RFS (P = 0.002) and DMFS (P < 0.001) among the four adjuvant therapy groups. The group receiving targeted therapy in conjunction with immunotherapyexhibited the longest median RFS and DMFS (both 30.0 months, 95% CI: 16.9–NR), while the D/T group did not reach a median. The PD-1 monotherapy group demonstrated lower RFS rates compared to the D/T group, although DMFS rates were comparable. The D/T group exhibited favorable RFS and DMFS rates, with both exceeding 50% at the three-year mark. Conclusions: The findings of this study indicate that adjuvant therapy with dabrafenib and trametinib (D/T) may represent the optimal treatment strategy for high-risk Chinese melanoma patients harboring BRAF mutations. Prolonging D/T treatment beyond one year appears to confer additional benefits. HDI and PD-1 monotherapy exhibited moderate efficacy in controlling recurrence, while targeted therapy effectively reduced local recurrence rates. Although immunotherapy demonstrated limitations in managing early local recurrence, it significantly mitigated the risk of distant metastasis in responsive patients. For individuals unable to tolerate the short-term adverse effects associated with dual-targeted therapy, a combination of targeted therapy and immunotherapy may present a viable alternative, yielding substantial RFS and DMFS advantages. However, the persistent adverse effects associated with PD-1 therapy necessitate vigilant monitoring.