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辅助治疗和 III 期黑色素瘤患者的结局:多中心真实世界德国皮肤肿瘤协作组(DeCOG)研究的结果。

Adjuvant treatment and outcome of stage III melanoma patients: Results of a multicenter real-world German Dermatologic Cooperative Oncology Group (DeCOG) study.

机构信息

Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Northrhine-Westphalia, Germany.

Department of Dermatology, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany.

出版信息

Eur J Cancer. 2023 Sep;191:112957. doi: 10.1016/j.ejca.2023.112957. Epub 2023 Jun 22.

Abstract

PURPOSE

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.

PATIENTS AND METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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%。

结论

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。

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