Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.
Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.
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DOI：
10.1158/2326-6066.cir-16-0325
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发表时间：
2017-05
影响因子：
10.1
通讯作者：
Daud A
中科院分区：
文献类型：
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作者：
Tumeh PC;Hellmann MD;Hamid O;Tsai KK;Loo KL;Gubens MA;Rosenblum M;Harview CL;Taube JM;Handley N;Khurana N;Nosrati A;Krummel MF;Tucker A;Sosa EV;Sanchez PJ;Banayan N;Osorio JC;Nguyen-Kim DL;Chang J;Shintaku IP;Boasberg PD;Taylor EJ;Munster PN;Algazi AP;Chmielowski B;Dummer R;Grogan TR;Elashoff D;Hwang J;Goldinger SM;Garon EB;Pierce RH;Daud A
我们探讨了肝转移、肿瘤CD 8 + T细胞计数与抗PD-1抗体pembrolizumab治疗的黑色素瘤或肺癌患者的应答之间的相关性。黑色素瘤发现队列来自I期Keynote 001试验，而黑色素瘤验证队列来自Keynote 002、006和EAP试验，非小细胞肺癌（NSCLC）队列来自Keynote 001。与无肝转移的患者（ORR，56.3%;中位PFS，20.1个月）相比，肝转移与缓解降低和无进展生存期缩短相关[PFS;客观缓解率（ORR），30.6%;中位PFS，5.1个月]，P ≤ 0.0001，并在验证队列中得到证实（P = 0.0006）。肝转移的存在显著增加了进展的可能性（OR，1.852; P < 0.0001）。在一部分活检患者（n = 62）中，肝转移与浸润性肿瘤边缘CD 8 + T细胞密度降低相关（肝转移+组，n = 547 ± 164.8;肝转移−组，n = 1，441 ± 250.7; P < 0.016）。与无肝转移的NSCLC患者（n = 119，中位PFS，4. 0个月; 95% CI，2. 1 - 5. 1）相比，在有肝转移的NSCLC患者中也观察到缓解率降低和PFS缩短[中位PFS，1. 8个月; 95% CI，1. 4 - 2. 0]，P = 0. 0094。因此，接受帕博利珠单抗治疗的黑色素瘤或NSCLC肝转移患者与缓解和PFS降低相关，肝转移与边缘CD 8 + T细胞浸润减少相关，为该结局提供了潜在机制。
We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non–small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis− group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4–2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1–5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome.