Majidova Nargiz, Arak Hacı, Ozalp Faruk Recep, Bas Onur, Koker Gulhan Ozcelik, Ozmarasalı Erkan Buket, Karateke Yasemin Sagdıc, Sakalar Teoman, Yaslikaya Sendag, Onur Ilknur Deliktas, Akdag Goncagul, Ogul Ali, Guliyev Murad, Sahin Elif, Delipoyraz Ebru Engin, Alkan Ali, Aydın Okan, Ilhan Nurullah, Alan Ozkan, Akbas Sinem, Cağlar Yaprak, Guren Ali Kaan, Sever Nadiye, Ellez Halil Ibrahim, Selcukbiricik Fatih, Muhammed Atcı Mustafa, Bilici Ahmet, Demirci Nebi Serkan, Basoglu Tugba, Karacin Cengiz, Kara Ismail Oguz, Yıldız Bulent, Evrensel Turkkan, Karaca Mustafa, Dizdar Omer, Atag Elif, Ozgun Alpaslan, Kostek Osman
Division of Medical Oncology, VM Medical Park Maltepe Hospital, Istanbul, Turkey.
Division of Medical Oncology, Gaziantep City Hospital, Gaziantep, Turkey.
Sci Rep. 2025 Jan 25;15(1):3200. doi: 10.1038/s41598-025-87553-z.
Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023. Data on clinicopathologic characteristics, treatment regimens and outcomes were collected. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Patients treated with dabrafenib plus trametinib as adjuvant therapy had the longest relapse-free survival (RFS) (median: 8.3 months), followed by those treated with interferon (4.1 months) and nivolumab (1.9 months) (p = 0.002). Metastatically, the highest ORR was observed in patients treated with dabrafenib plus trametinib (54.5%), followed by ICI (52.0%) and chemotherapy (33.3%). Similarly, DCR was superior for dabrafenib plus trametinib (86.3%) compared to ICI (70.8%) and chemotherapy (66.6%). Median PFS was 9.7 months (95% CI 7.2-12.2 months) in the whole group. This was 14.3 months (95% CI 9.6-19.0 months) with ICI, 10.3 months (95% CI 4.2-16.4 months) with BRAF/MEK inhibitors and 6.3 months (95% CI 4.7-7.9 months) with chemotherapy, which was statistically significant (p < 0.001). Dabrafenib plus trametinib showed the longest median OS (53.5 months) in metastatic patients and was significantly better than chemotherapy (33.6 months) (p < 0.001). BRAF V600E mutation, RFS > 6 months, ORR are all independent factors for OS prognosis. In our study, dabrafenib plus trametinib combination was more effective in adjuvant treatment of melanoma, while immunotherapy was more effective in metastatic first-line treatment.
随着靶向治疗和免疫检查点抑制剂（ICI）的发现，黑色素瘤的治疗发生了显著变化。我们这项研究的目的是确定哪些治疗方案，特别是达拉非尼联合曲美替尼和ICI，在辅助治疗中有效，以及哪种治疗作为一线转移性治疗有效。这项回顾性多中心研究纳入了120例在2007年至2023年间被诊断为IIIB-IIID期黑色素瘤且接受辅助治疗和一线转移性治疗的患者。收集了临床病理特征、治疗方案和结局的数据。分析了客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。接受达拉非尼联合曲美替尼作为辅助治疗的患者无复发生存期（RFS）最长（中位数：8.3个月），其次是接受干扰素治疗的患者（4.1个月）和纳武利尤单抗治疗的患者（1.9个月）（p = 0.002）。在转移性治疗中，接受达拉非尼联合曲美替尼治疗的患者ORR最高（54.5%），其次是ICI（52.0%）和化疗（33.3%）。同样，达拉非尼联合曲美替尼的DCR（86.3%）优于ICI（70.8%）和化疗（66.6%）。全组的中位PFS为9.7个月（95%CI 7.2 - 12.2个月）。ICI治疗时为14.3个月（95%CI 9.6 - 19.0个月），BRAF/MEK抑制剂治疗时为10.3个月（95%CI 4.2 - 16.4个月），化疗时为6.3个月（95%CI 4.7 - 7.9个月），差异有统计学意义（p < 0.001）。达拉非尼联合曲美替尼在转移性患者中显示出最长的中位OS（53.5个月），且显著优于化疗（33.6个月）（p < 0.001）。BRAF V600E突变、RFS>6个月、ORR均为OS预后的独立因素。在我们的研究中，达拉非尼联合曲美替尼方案在黑色素瘤辅助治疗中更有效，而免疫治疗在转移性一线治疗中更有效。
