Ghatalia Pooja, Zibelman Matthew, Geynisman Daniel M, Plimack Elizabeth R
Department of Hematology/Oncology, Fox Chase Cancer Center, Temple Health, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.
Curr Treat Options Oncol. 2017 Jan;18(1):7. doi: 10.1007/s11864-017-0458-0.
The advent of checkpoint inhibitors has revolutionized systemic therapy for many malignancies, including renal cell carcinoma (RCC) where multiple PD-1, PD-L1, and CTLA-4 inhibitors have demonstrated responses and improved survival for patients in clinical trials. Durable benefit with manageable toxicity can be achieved with these agents-but unfortunately for only a minority of individuals. Efforts are ongoing to understand mechanisms driving the response and resistance to checkpoint inhibitors in order to personalize therapy and extend benefit to more patients. In particular, combination immunotherapy is an area of active study with multiple ongoing trials in RCC. Novel immunotherapeutic agents are being explored as well. Clinically, there are nuances related to the use of immunotherapy that are important to understand in order to provide optimal care to patients. Potential autoimmune toxicities are important to identify early so they can be best mitigated with immunosuppression, and careful review of imaging with clinical correlation is important to ensure responding patients are not taken off treatment prematurely due to "pseudo-progression." Lastly, although immunotherapy is an important new tool, it exists among other active agents in the treatment of RCC, and further study is needed to understand where it best fits in the treatment paradigm. In this article, we review the most recent data for immune checkpoint inhibitors in metastatic renal cell carcinoma and more broadly discuss the rapidly evolving landscape of immunotherapy in RCC, including combination immunotherapies.
检查点抑制剂的出现彻底改变了许多恶性肿瘤的全身治疗，包括肾细胞癌（RCC），在临床试验中，多种PD - 1、PD - L1和CTLA - 4抑制剂已显示出对患者的疗效并改善了生存情况。使用这些药物可以实现具有可管理毒性的持久获益——但遗憾的是，只有少数患者能从中受益。目前正在努力了解驱动对检查点抑制剂产生反应和耐药的机制，以便实现个性化治疗并使更多患者受益。特别是，联合免疫疗法是一个正在积极研究的领域，在RCC中有多项正在进行的试验。新型免疫治疗药物也在探索之中。在临床上，了解免疫疗法使用过程中的细微差别对于为患者提供最佳治疗至关重要。潜在的自身免疫毒性需要尽早识别，以便通过免疫抑制措施将其降至最低，并且仔细结合临床情况审查影像学检查对于确保有反应的患者不会因“假性进展”而过早停止治疗很重要。最后，尽管免疫疗法是一种重要的新工具，但它在RCC的治疗中与其他有效药物并存，需要进一步研究以了解其在治疗模式中最适合的位置。在本文中，我们回顾了转移性肾细胞癌中免疫检查点抑制剂的最新数据，并更广泛地讨论了RCC中免疫疗法快速演变的情况，包括联合免疫疗法。
