在免疫肿瘤学时代,抗PD-1或抗PD-L1免疫疗法是否正在改变对传统癌症疗法的敏感性?
In the immuno-oncology era, is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies?
作者信息
Aspeslagh Sandrine, Matias Margarida, Palomar Virginia, Dercle Laurent, Lanoy Emilie, Soria Jean-Charles, Postel-Vinay Sophie
机构信息
Gustave Roussy, Département D'Innovation Thérapeutique et Essais Précoces, Villejuif, France.
Gustave Roussy, Département de Médecine Oncologique, Villejuif, France.
出版信息
Eur J Cancer. 2017 Dec;87:65-74. doi: 10.1016/j.ejca.2017.09.027. Epub 2017 Nov 7.
INTRODUCTION
The advent of anti-programmed death receptor-1/ligand-1 antibodies (anti-PD(L)1) is profoundly changing the therapeutic strategy of oncology. As anti-PD(L)1 modulate tumour microenvironment, it might impact sensitivity to conventional cancer therapy (CCT). Therefore, we explored whether sensitivity to CCT was different before and after anti-PD(L)1 therapy.
METHODS
Patients who started anti-PD(L)1 treatment at Gustave Roussy Cancer Centre between February 2012 and December 2015, and who received at least one line of CCT immediately before and immediately after anti-PD(L)1, were eligible. We analysed progression-free survival (PFS) and overall response rate (ORR) of the CCT line immediately before (PFSpre/ORRpre) and after (PFSpost/ORRpost) anti-PD(L)1. PFS and ORR were compared using Wilcoxon signed rank and McNemar tests in a paired data subset for patients having received identical class of CCT pre and post anti-PD(L)1 therapy.
RESULTS
Among 118 eligible patients, 65% received anti-PD1 and 35% anti-PD-L1 agents. Median PFSpre versus PFSpost was 4.7 versus 3.5 months (p = 0.011), respectively; it was 5.7 versus 6.8 months (NS) for patients who derived clinical benefit from immunotherapy and 3.9 versus 3.0 months (p = 0.012) for patients who were primary resistant to anti-PD(L)1 therapy. Subgroup analysis did not reveal any significant difference in PFS or ORR before versus after anti-PD(L)1 therapy according to CCT class or to its ability to induce immunogenic cell death.
CONCLUSION
Patients who derive benefit from immune therapies tend to have better PFS on conventional therapies after having received the anti-PD(L)1 agent. Further studies on larger data sets are warranted to confirm these findings.
引言
抗程序性死亡受体-1/配体-1抗体(抗PD(L)1)的出现正在深刻改变肿瘤学的治疗策略。由于抗PD(L)1可调节肿瘤微环境,它可能会影响对传统癌症治疗(CCT)的敏感性。因此,我们探讨了抗PD(L)1治疗前后对CCT的敏感性是否存在差异。
方法
2012年2月至2015年12月期间在古斯塔夫·鲁西癌症中心开始接受抗PD(L)1治疗,且在抗PD(L)1治疗前后均接受至少一线CCT的患者符合条件。我们分析了抗PD(L)1治疗前(PFSpre/ORRpre)和治疗后(PFSpost/ORRpost)CCT疗程的无进展生存期(PFS)和总缓解率(ORR)。对于抗PD(L)1治疗前后接受相同类型CCT的患者,在配对数据子集中使用Wilcoxon符号秩检验和McNemar检验比较PFS和ORR。
结果
在118例符合条件的患者中,65%接受抗PD1治疗,35%接受抗PD-L1药物治疗。PFSpre与PFSpost的中位数分别为4.7个月和3.5个月(p = 0.011);从免疫治疗中获得临床益处的患者为5.7个月和6.8个月(无显著性差异),对抗PD(L)1治疗原发耐药的患者为3.9个月和3.0个月(p = 0.012)。亚组分析未发现根据CCT类型或其诱导免疫原性细胞死亡能力,抗PD(L)1治疗前后的PFS或ORR有任何显著差异。
结论
从免疫治疗中获益的患者在接受抗PD(L)1药物治疗后,在传统治疗中往往有更好的PFS。有必要对更大的数据集进行进一步研究以证实这些发现。