Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Northrhine-Westphalia, Germany.
Department of Dermatology, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany.
Eur J Cancer. 2023 Sep;191:112957. doi: 10.1016/j.ejca.2023.112957. Epub 2023 Jun 22.
Clinical trials demonstrated significantly improved recurrence-free survival (RFS) of melanoma patients receiving adjuvant treatment. As data from controlled trials are based on selected populations, we investigated adjuvantly treated stage III melanoma patients under real-world conditions.
In a prior multicenter cohort study, stage III-IV melanoma patients were analysed for their choice of adjuvant therapy. In this follow-up study, we examined RFS, overall and melanoma-specific survival (MSS) and response to the subsequent treatment of 589 stage III patients (232 BRAF-mutated) receiving adjuvant PD-1 inhibitors (PD1; n = 479) or targeted therapy (TT; n = 110).
The median follow-up of the total cohort was 25.7 months. The main reason for premature discontinuation of adjuvant therapy was disease progression in PD1- (28.8%, n = 138/479) and adverse events in TT-treated patients (28.2%, n = 31/110). Among BRAF-mutated patients, RFS at 24 months was 49% (95% CI 40.6-59.0%) for PD1- and 67% (95% CI 58-77%) for TT-treated patients. The risk of recurrence was higher for BRAF-mutated PD1 than TT (hazard ratio 1.99; 95% CI 1.34-2.96; hazard ratio adjusted for age, sex and tumour stage, 2.21; 95% CI 1.48-3.30). Twenty-four months MSS was 87% (95% CI 81.0-94.1) for PD1 and 92% (95% CI 86.6-97.0) for TT. Response to subsequent systemic treatment for unresectable disease was 22% for all PD1- and 16% for TT-treated patients.
PD1-treated patients had more and earlier recurrences than TT patients. In BRAF-mutated patients, adjuvant TT might prevent early recurrences more effectively than PD1 treatment. Management of recurrence despite adjuvant treatment is challenging, with low response to current therapeutic options.
临床试验表明,接受辅助治疗的黑色素瘤患者的无复发生存率(RFS)显著提高。由于对照试验的数据基于选定的人群,因此我们在真实环境下研究了接受辅助治疗的 III 期黑色素瘤患者。
在之前的一项多中心队列研究中,分析了 III-IV 期黑色素瘤患者选择辅助治疗的情况。在这项随访研究中,我们检查了 589 例接受辅助 PD-1 抑制剂(PD1;n=479)或靶向治疗(TT;n=110)的 III 期患者(232 例 BRAF 突变)的 RFS、总生存期(OS)和黑色素瘤特异性生存期(MSS)以及对后续治疗的反应。
总队列的中位随访时间为 25.7 个月。PD1 组(28.8%,n=138/479)和 TT 组(28.2%,n=31/110)中辅助治疗过早停止的主要原因是疾病进展和不良事件。在 BRAF 突变患者中,PD1 组和 TT 组 24 个月的 RFS 分别为 49%(95%CI 40.6-59.0%)和 67%(95%CI 58-77%)。BRAF 突变的 PD1 组比 TT 组复发风险更高(危险比 1.99;95%CI 1.34-2.96;经年龄、性别和肿瘤分期调整的危险比,2.21;95%CI 1.48-3.30)。PD1 组和 TT 组 24 个月的 MSS 分别为 87%(95%CI 81.0-94.1)和 92%(95%CI 86.6-97.0)。对于不可切除疾病的后续系统性治疗,PD1 组和 TT 组的应答率分别为 22%和 16%。
PD1 治疗组比 TT 治疗组有更多且更早的复发。在 BRAF 突变患者中,辅助 TT 可能比 PD1 治疗更有效地预防早期复发。尽管进行了辅助治疗,但对复发的管理仍然具有挑战性,目前的治疗选择应答率较低。