Checkpoint inhibition in advanced gastroesophageal cancer: clinical trial data, molecular subtyping, predictive biomarkers, and the potential of combination therapies.

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY Translational gastroenterology and hepatology Pub Date : 2019-08-27 eCollection Date: 2019-01-01 DOI:10.21037/tgh.2019.08.04
Jeremy Chuang, Joseph Chao, Andrew Hendifar, Samuel J Klempner, Jun Gong
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Abstract

The development of checkpoint inhibitors has redefined the treatment paradigm for advanced gastroesophageal cancer. While recent developments have improved clinical outcomes, the prognosis for the disease remains meager. In this review, we discuss the rationale and detail the results from recent phase I-III trials supporting the activity of PD-1 inhibitors. Specifically, we highlight the seminal clinical trials leading to the FDA approval of pembrolizumab for advanced gastroesophageal cancer. Finally, we review the current understanding and future considerations of molecular subtyping and predictive biomarkers to help guide therapy and the promise of combination therapy to further improve the efficacy of checkpoint inhibitors.

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晚期癌症的检查点抑制:临床试验数据、分子亚型、预测性生物标志物和联合治疗的潜力。
检查点抑制剂的发展重新定义了晚期癌症的治疗模式。尽管最近的进展改善了临床结果,但该疾病的预后仍然很差。在这篇综述中,我们讨论了支持PD-1抑制剂活性的最新I-III期试验的基本原理和详细结果。具体而言,我们强调了导致FDA批准pembrolizumab治疗晚期癌症的开创性临床试验。最后,我们回顾了目前对分子亚型和预测性生物标志物的理解和未来的考虑,以帮助指导治疗,以及联合治疗进一步提高检查点抑制剂疗效的前景。
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