帕博利珠单抗治疗后伊匹单抗或 BRAF±MEK 抑制治疗晚期黑色素瘤患者的抗肿瘤活性：KEYNOTE-006 的分析结果。
Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006.
机构信息
Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine & Health, The University of Sydney, Sydney, Australia; Charles Perkins Centre, The University of Sydney, Sydney, Australia; Royal North Shore and Mater Hospital, Sydney, Australia.
Hospital Clinic de Barcelona and IDIBAPS, Barcelona, Spain.
出版信息
Ann Oncol. 2022 Feb;33(2):204-215. doi: 10.1016/j.annonc.2021.10.010. Epub 2021 Oct 25.
BACKGROUND
Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized.
PATIENTS AND METHODS
In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi ± MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled.
RESULTS
At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi ± MEKi for 59 (10.6%) [33 received BRAFi + MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi ± MEKi naïve]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi ± MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi ± MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi ± MEKi initiation was 12.9 months. ORR for BRAFi ± MEKi-naïve patients who received subsequent BRAFi ± MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR).
CONCLUSIONS
Ipilimumab and BRAFi ± MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.
背景
在黑色素瘤患者接受帕博利珠单抗治疗后，使用伊匹单抗或 BRAF ± MEK 抑制剂（BRAFi ± MEKi）的抗肿瘤活性特征描述不佳。
患者和方法
在 III 期 KEYNOTE-006 研究中，不可切除的 III/IV 期黑色素瘤患者接受帕博利珠单抗（10mg/kg）每 2 或 3 周（Q3W）一次或伊匹单抗（3mg/kg）Q3W。本事后分析评估了帕博利珠单抗治疗后使用伊匹单抗或 BRAFi ± MEKi 作为一线后续全身治疗的结果，包括已完成或停止使用一剂以上帕博利珠单抗的患者。帕博利珠单抗组被汇总。
结果
在数据截止日期（2017 年 12 月 4 日），中位随访时间为 46.9 个月。在 555 名接受帕博利珠单抗治疗的患者中，一线后续治疗为伊匹单抗 103 例（18.6%）和 BRAFi ± MEKi 59 例（10.6%）[33 例接受 BRAFi+MEKi，26 例接受 BRAFi 单药治疗；37 例（62.7%）为 BRAFi ± MEKi 初治]。在随后的伊匹单抗组中，先前接受帕博利珠单抗治疗的客观缓解率（ORR）为 17.5%[1 例完全缓解（CR）；17 例部分缓解（PR）]；79.6%因疾病进展（PD）而停止使用帕博利珠单抗；中位总生存期（OS）为 21.5 个月。随后伊匹单抗治疗的 ORR 为 15.5%；16 例应答中有 11 例（8 例 CR；3 例 PR）仍在继续。先前对帕博利珠单抗的最佳反应为 PD 的患者，随后使用伊匹单抗的 ORR 为 9.7%。从伊匹单抗开始治疗的中位 OS 为 9.8 个月。在随后的 BRAFi ± MEKi 组中，先前接受帕博利珠单抗治疗的 ORR 为 13.5%（8 例 PR）；76.3%因 PD 而停止使用帕博利珠单抗；中位 OS 为 17.9 个月。随后接受 BRAFi ± MEKi 治疗的 ORR 为 30.5%，18 例应答中有 7 例（4 例 CR，3 例 PR）仍在继续。从 BRAFi ± MEKi 开始治疗的中位 OS 为 12.9 个月。先前接受过 BRAFi ± MEKi 治疗且随后接受 BRAFi ± MEKi 治疗的 BRAFi ± MEKi 初治患者的 ORR 为 43.2%；16 例中有 6 例仍在继续（3 例 CR，3 例 PR）。
结论
伊匹单抗和 BRAFi ± MEKi 在黑色素瘤患者中作为帕博利珠单抗治疗后的一线后续治疗具有抗肿瘤活性。
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