Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Curr Opin Oncol. 2018 Sep;30(5):345-351. doi: 10.1097/CCO.0000000000000466.
The advent of immunotherapy significantly improved clinical outcomes in cancer patients, although immune checkpoint blockade (ICB) still lack of efficacy in a consistent proportion of treated patients. The purpose of this article is to review the most innovative and clinically promising ICB-based combinations designed to improve the efficacy of cancer immunotherapy.
First-line combinatorial treatment with ipilimumab and nivolumab has recently shown to be superior to the standard of care in a subset of metastatic nonsmall cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The combination of programmed cell death protein 1 (PD-1)/PD-L1 blockade with antiangiogenics has demonstrated a consistent clinical efficacy, especially for the combination of bevacizumab and atezolizumab as first-line therapy in metastatic RCC. The sequential combination of definitive chemoradiotherapy followed by durvalumab maintenance in advanced, unresectable NSCLC became the new standard of care, while the addition of pembrolizumab to first-line chemotherapy in metastatic NSCLC significantly improves overall survival. Despite promising results for the combination of ICBs with v-raf murine sarcoma viral oncogene homolog B/MAPK/ERK kinase inhibitors or epidermal growth factor receptor inhibitors, especially in melanoma and NSCLC, safety concerns slowed down the development of such strategies.
Immunotherapy-based combinations are becoming the standard of care for cancer treatment, in particularly for advanced melanoma, NSCLC and RCC.
综述目的:免疫疗法的出现显著改善了癌症患者的临床结局,但免疫检查点阻断(ICB)在相当一部分接受治疗的患者中仍然缺乏疗效。本文旨在综述基于 ICB 的最具创新性和最有临床前景的联合治疗方案,以提高癌症免疫治疗的疗效。
最新发现:Ipilimumab 和 nivolumab 的一线联合治疗最近在转移性非小细胞肺癌(NSCLC)和肾细胞癌(RCC)的亚组中显示出优于标准治疗的疗效。程序性死亡蛋白 1(PD-1)/PD-L1 阻断与抗血管生成药物的联合应用具有一致的临床疗效,特别是贝伐珠单抗联合 atezolizumab 作为转移性 RCC 的一线治疗。在晚期不可切除的 NSCLC 中,确定性放化疗后序贯 durvalumab 维持治疗成为新标准,而在转移性 NSCLC 中,将 pembrolizumab 加入一线化疗中显著提高了总生存期。尽管 ICB 联合 v-raf 鼠肉瘤病毒致癌基因同源物 B/MAPK/ERK 激酶抑制剂或表皮生长因子受体抑制剂的联合治疗方案在黑色素瘤和 NSCLC 中显示出良好的疗效,但安全性问题减缓了这些策略的发展。
总结:基于免疫疗法的联合治疗正在成为癌症治疗的标准方案,特别是在晚期黑色素瘤、NSCLC 和 RCC 中。