先前使用免疫检查点抑制剂治疗对转移性黑色素瘤达卡巴嗪疗效的影响。
Impact of prior treatment with immune checkpoint inhibitors on dacarbazine efficacy in metastatic melanoma.
机构信息
Department of General and Oncologic Dermatology, Ambroise Paré Hospital, AP-HP, Boulogne-Billancourt, France.
Research unit EA4340 'Biomarkers and clinical trials in cancerology and onco-hematology', Versailles-Saint-Quentin-en-Yvelines University, Paris-Saclay University, Boulogne-Billancourt, France.
出版信息
Br J Cancer. 2021 Sep;125(7):948-954. doi: 10.1038/s41416-021-01486-8. Epub 2021 Jul 14.
BACKGROUND
Despite its low efficacy, chemotherapy with dacarbazine remains an option in metastatic melanoma patients after failure of immune checkpoint inhibitors (ICI) ± targeted therapy. Some observations suggested an increased efficacy of chemotherapy in melanoma or lung cancer patients previously treated with ICI; we aimed to evaluate the efficacy of dacarbazine in a controlled-group study of patients pre-treated or not with ICI.
METHODS
We retrospectively collected data from all consecutive patients treated with dacarbazine for advanced cutaneous melanoma without brain metastasis, in our skin cancer centre between June 2006 and September 2019. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rates (ORR), overall survival (OS) and safety of dacarbazine.
RESULTS
Among 72 patients, 17 (23.6%) received dacarbazine after ICI and 55 (76.3%) without prior ICI. Despite less favourable prognostic factors in patients ICI-pre-treated, median PFS was 4.27 months (range 0.89-43.69) in this group versus 2.04 months (range 1.25-39.25) P = 0.03 in non-ICI-pre-treated patients; ORR were 35.3% and 12.7%, respectively. The median OS and the occurrence of adverse events were similar in both groups.
CONCLUSION
Dacarbazine seems to offer a short-lived benefit in patients with progressive advanced disease despite ICI (±targeted therapy), and could be an alternative before considering best supportive care.
背景
尽管达卡巴嗪化疗的疗效较低，但在免疫检查点抑制剂（ICI）±靶向治疗失败的转移性黑色素瘤患者中，它仍是一种选择。一些观察结果表明，在先前接受 ICI 治疗的黑色素瘤或肺癌患者中，化疗的疗效有所提高；我们旨在评估达卡巴嗪在一项对照研究中对预先接受或未接受 ICI 治疗的患者的疗效。
方法
我们回顾性地收集了 2006 年 6 月至 2019 年 9 月期间在我们皮肤癌中心接受达卡巴嗪治疗的无脑转移晚期皮肤黑色素瘤的所有连续患者的数据。主要终点是无进展生存期（PFS）；次要终点是总缓解率（ORR）、总生存期（OS）和达卡巴嗪的安全性。
结果
在 72 例患者中，17 例（23.6%）在接受 ICI 后接受了达卡巴嗪治疗，55 例（76.3%）在接受 ICI 前未接受过治疗。尽管 ICI 预处理患者的预后因素较差，但该组的中位 PFS 为 4.27 个月（范围 0.89-43.69），而未接受 ICI 预处理的患者为 2.04 个月（范围 1.25-39.25），P=0.03；ORR 分别为 35.3%和 12.7%。两组的中位 OS 和不良事件的发生情况相似。
结论
尽管存在 ICI（±靶向治疗），达卡巴嗪在进展性晚期疾病患者中似乎提供了短暂的益处，并且可以在考虑最佳支持治疗之前作为替代方案。
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