EORTC1325/KEYNOTE-054 试验中辅助性帕博利珠单抗对比安慰剂用于 III 期黑色素瘤的 7 年分析。
Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial.
机构信息
Comprehensive Cancer Center Munich of the Technical University Munich and the Ludwig Maximilians University, Munich, Germany; Princess Máxima Center and University Medical Center Utrecht, Utrecht, the Netherlands.
EORTC Headquarters, Brussels, Belgium.
出版信息
Eur J Cancer. 2024 Nov;211:114327. doi: 10.1016/j.ejca.2024.114327. Epub 2024 Sep 12.
UNLABELLED
In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up.
METHODS
We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for the PD-1 ligand (PD-L1) were co-primary endpoints. DMFS in these two populations was a secondary and progression/recurrence-free survival 2 (PRFS2) an exploratory endpoint.
RESULTS
The median follow-up was 6.9 years. In the overall intention-to-treat population, RFS was longer in the pembrolizumab group than in the placebo group (HR 0.63, 95 % CI 0.53 to 0.74). RFS at 7 years was 50 % (95 % CI 46 % to 55 %) in the pembrolizumab and 36 % (95 % CI 32 % to 41 %) in the placebo group. Positive effects were present both for loco-regional recurrences and distant metastases, and across substages IIIA-IIIB-IIIC, and PD-L1 positive and PD-L1 negative as well as for BRAF mutant and BRAF wild type populations. DMFS was longer in the pembrolizumab group than in the placebo group (HR 0.64, 95 % CI 0.54 to 0.76). DMFS at 7 years was 54 % (95 % CI 50 % to 59 %) in the pembrolizumab and 42 % (95 % CI 37 % to 46 %) in the placebo group. PRFS2 was longer in the pembrolizumab group than in the placebo group (HR 0.69, 95 % CI 0.57 to 0.84). PRFS2 at 7 years was 61 % (95 % CI 57 % to 66 %) in the pembrolizumab and 53 % (95 % CI 49 % to 57 %) in the placebo group.
CONCLUSIONS
The 7-year analysis of adjuvant therapy with pembrolizumab demonstrated a sustained improvement in the long-term RFS, DMFS and PRFS2 compared with placebo in patients with resected stage III melanoma.
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在这项 3 期试验的先前报告的主要分析中，与安慰剂相比，接受辅助 pembrolizumab 治疗 12 个月的患者，其无复发生存期（RFS）和远处转移无复发生存期（DMFS）显著延长，这些益处的稳定性在中位随访 3.5 年和 5 年时得到了发表。在此，我们报告了更长随访时间的结果。
方法
我们将 1019 名患者随机分配接受 pembrolizumab 200mg 或安慰剂，静脉注射，每 3 周一次，共 18 剂。总体人群和 PD-1 配体（PD-L1）阳性黑色素瘤患者亚组的 RFS 是共同的主要终点。这两个人群的 DMFS 是次要终点，进展/复发无进展生存 2 期（PRFS2）是探索性终点。
结果
中位随访时间为 6.9 年。在总体意向治疗人群中，与安慰剂组相比，pembrolizumab 组的 RFS 更长（HR 0.63，95%CI 0.53 至 0.74）。pembrolizumab 组和安慰剂组的 7 年 RFS 分别为 50%（95%CI 46%至 55%）和 36%（95%CI 32%至 41%）。局部区域复发和远处转移均有积极效果，亚组 IIIA-IIIB-IIIC 以及 PD-L1 阳性和 PD-L1 阴性以及 BRAF 突变和 BRAF 野生型人群也有积极效果。与安慰剂组相比，pembrolizumab 组的 DMFS 更长（HR 0.64，95%CI 0.54 至 0.76）。pembrolizumab 组和安慰剂组的 7 年 DMFS 分别为 54%（95%CI 50%至 59%）和 42%（95%CI 37%至 46%）。与安慰剂组相比，pembrolizumab 组的 PRFS2 更长（HR 0.69，95%CI 0.57 至 0.84）。pembrolizumab 组和安慰剂组的 7 年 PRFS2 分别为 61%（95%CI 57%至 66%）和 53%（95%CI 49%至 57%）。
结论
pembrolizumab 辅助治疗的 7 年分析显示，与安慰剂相比，接受辅助 pembrolizumab 治疗的 III 期黑色素瘤患者的 RFS、DMFS 和 PRFS2 长期持续改善。
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