Grover P, Lo S N, Li I, Kuijpers A M J, Kreidieh F, Williamson A, Amaral T, Dimitriou F, Placzke J, Olino K, Vitale M G, Saiag P, Gutzmer R, Allayous C, Olofsson Bagge R, Mattsson J, Asher N, Carter T J, Meniawy T M, Lawless A R, Czapla J A, Warburton L, Gaudy-Marqueste C, Grob J J, Collins R G, Zhang E, Kessels J I, Neyns B, Mehmi I, Hamid O, Julve M, Furness A J S, Margolin K A, Lev-Ari Shaked, Ressler J M, Haque W, Khattak M A, Wicky A, Roberts-Thomson R, Arance A, Warrier G, Schollenberger M D, Parente P, Chatziioannou E, Lipson E J, Michielin O, Weber J S, Hoeller C, Larkin J, Atkins M B, Essner R, Johnson D B, Sullivan R J, Nathan P, Schachter J, Lebbe C, Ascierto P A, Kluger H, Rutkowski P, Dummer R, Garbe C, Lorigan P C, Burton E, Tawbi H A, Haanen J, Carlino M S, Menzies A M, Long G V
Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Ann Oncol. 2025 Jul;36(7):807-818. doi: 10.1016/j.annonc.2025.03.021. Epub 2025 Apr 8.
Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.
In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined.
A total of 628 patients from 34 centres across Australia, Europe and the United States were identified-256 in anti-PD-1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (interquartile range 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD-1 compared with OBS. The 2-year RFS was 79.3% [95% confidence interval (CI) 74.1% to 84.8%] for anti-PD-1, 98.6% (95% CI 96.0% to 100%) for TT and 84.3% (95% CI 79.9% to 89.0%) for OBS. The 2-year DMFS was 88.4% (95% CI 84.3% to 92.8%) in anti-PD-1, 100% in TT and 91.1% (95% CI 87.7% to 94.7%) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in anti-PD-1 and OBS (P < 0.05). Rates of ≥grade 3 toxicities were 10.9% with anti-PD-1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in the anti-PD-1 group and 12.5% in the TT group.
Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD-1 did not significantly improve RFS or DMFS compared with OBS alone. Adjuvant TT appears promising over anti-PD-1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow-up or prospective randomised trials.
在辅助药物治疗的临床试验中，接受美国癌症联合委员会第八版（AJCC v8）IIIA期黑色素瘤切除术的患者代表性不足。辅助靶向治疗和免疫治疗在该人群中的益处尚不清楚。
在这项多中心回顾性研究中，纳入了接受辅助派姆单抗或纳武单抗[抗程序性细胞死亡蛋白1（PD-1）]、BRAF/MEK靶向治疗达拉非尼+曲美替尼（TT）或未接受辅助治疗[观察（OBS）]的IIIA期黑色素瘤（AJCC v8）患者。检查无复发生存期（RFS）、无远处转移生存期（DMFS）和毒性发生率。
共确定了来自澳大利亚、欧洲和美国34个中心的628例患者——抗PD-1组256例，TT组80例，OBS组292例。中位随访时间为2.6年（四分位间距1.6 - 3.4年）。与OBS组相比，抗PD-1组中一些关键的不良预后变量的存在显著更高。抗PD-1组的2年RFS为79.3%[95%置信区间（CI）74.1%至84.8%]，TT组为98.6%（95%CI 96.0%至100%），OBS组为84.3%（95%CI 79.9%至89.0%）。抗PD-1组的2年DMFS为88.4%（95%CI 84.3%至92.8%），TT组为100%，OBS组为91.1%（95%CI 87.7%至94.7%）。在抗PD-1组和OBS组中，较高的Breslow厚度和较高的有丝分裂率与较高的复发风险相关（P < 0.05）。≥3级毒性发生率在抗PD-1组为10.9%，在TT组为17.5%；因毒性而停药的发生率分别为13.3%和21.2%。最后一次随访时未解决的毒性发生率在抗PD-1组为26.9%，在TT组为12.5%。
IIIA期黑色素瘤有适度的复发风险。与单独观察相比，辅助抗PD-1治疗并未显著改善RFS或DMFS。辅助TT治疗似乎比抗PD-1治疗或观察更有前景。该人群辅助治疗后的结果需要在更大的数据集、更长时间随访或前瞻性随机试验中进一步研究。
