Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma.
Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma.
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DOI：
10.1136/jitc-2021-002478
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发表时间：
2021-04
影响因子：
10.9
通讯作者：
Topalian SL
中科院分区：
文献类型：
--
作者：
Nghiem P;Bhatia S;Lipson EJ;Sharfman WH;Kudchadkar RR;Brohl AS;Friedlander PA;Daud A;Kluger HM;Reddy SA;Boulmay BC;Riker A;Burgess MA;Hanks BA;Olencki T;Kendra K;Church C;Akaike T;Ramchurren N;Shinohara MM;Salim B;Taube JM;Jensen E;Kalabis M;Fling SP;Homet Moreno B;Sharon E;Cheever MA;Topalian SL
默克尔细胞癌 (MCC) 是一种侵袭性皮肤癌，与较差的生存率相关。与 MCC 化疗相比，程序性细胞死亡 1 (PD-1) 通路抑制剂显示出较高的持久肿瘤消退率。目前的研究旨在评估与 MCC 消退和 3 年生存相关的基线和治疗中因素，并探讨癌症免疫治疗试验 Network-09/KEYNOTE-017 一线派姆单抗治疗后出现初始无反应或有反应或疾病稳定后出现肿瘤进展的患者的挽救治疗效果。在这项多中心 II 期试验中，50 名晚期不可切除 MCC 患者每 3 周接受 2 mg/kg 派姆单抗治疗，持续 ≤2 年。患者的随访时间中位数为 31.8 个月。派姆单抗的总体缓解率为 58%（完全缓解 30%+部分缓解 28%；95% CI 43.2 至 71.8）。在 29 名应答者中，中位应答持续时间 (NR) 在 3 年时尚未达到（范围 1.0+ 至 51.8+ 个月）。中位无进展生存期 (PFS) 为 16.8 个月（95% CI 4.6 至 43.4），3 年 PFS 为 39.1%。中位 OS 为 NR；所有患者的 3 年 OS 为 59.4%，应答者的 3 年 OS 为 89.5%。东部肿瘤合作组的基线表现状态为 0、肿瘤缩小百分比更大、完成 2 年治疗以及中性粒细胞与淋巴细胞比率较低与缓解和较长生存期相关。在最初出现疾病进展的患者或在缓解或疾病稳定后出现进展的患者中，一些患者通过包括化疗和免疫疗法在内的后续治疗延长了生存期。这项研究代表了 MCC 一线抗程序性死亡（配体）1（抗 PD-(L)1）治疗中最长的可用随访，证实了部分患者的持久 PFS 和 OS。在最初的肿瘤进展或缓解后复发后，一些接受挽救治疗的患者存活下来。改善抗 PD-(L)1 难治性 MCC 的管理仍然是一项挑战，也是一个高度优先事项。 NCT02267603。
Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017. In this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months. Overall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies. This study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority. NCT02267603.
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影响因子：
8.4
作者：
Ameratunga, Malaka;Chenard-Poirier, Maxime;Lopez, Juanita
通讯作者：
Lopez, Juanita
影响因子：
168.9
作者：
Engels, EA;Frisch, M;Miller, RW
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Miller, RW
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11.2
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Harms PW;Vats P;Verhaegen ME;Robinson DR;Wu YM;Dhanasekaran SM;Palanisamy N;Siddiqui J;Cao X;Su F;Wang R;Xiao H;Kunju LP;Mehra R;Tomlins SA;Fullen DR;Bichakjian CK;Johnson TM;Dlugosz AA;Chinnaiyan AM
通讯作者：
Chinnaiyan AM
影响因子：
10.1
作者：
Lipson EJ;Vincent JG;Loyo M;Kagohara LT;Luber BS;Wang H;Xu H;Nayar SK;Wang TS;Sidransky D;Anders RA;Topalian SL;Taube JM
通讯作者：
Taube JM
影响因子：
10.1
作者：
Jing, Lichen;Ott, Mariliis;Koelle, David M.
通讯作者：
Koelle, David M.