Faculty of Medicine, Saint Joseph University of Beirut, Riad El Solh, 11-5076, Beirut, 11072180, Lebanon.
Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University of Beirut, Riad El Solh, 11-5076, Beirut, 11072180, Lebanon.
Med Oncol. 2024 Sep 5;41(10):242. doi: 10.1007/s12032-024-02486-3.
In recent years, kidney cancer has shown an increased worldwide incidence of more than 400 000 novel cases annually. Although more than half of patients are diagnosed at a localised stage, this disease presents a high-risk of relapse after surgery. Thus, there is a need for adjuvant therapy post-resection to reduce cancer recurrence and prolong disease-free and overall survival. Thorough investigation of adjuvant drugs for renal cell carcinoma (RCC) has shown little promise in the last fifty years, with no recorded overall survival benefits. This was the case until pembrolizumab, an immune checkpoint inhibitor, was introduced into the adjuvant RCC space through the KEYNOTE-564 trial. The adjuvant administration of this novel anti-PD-1 drug demonstrated a significant overall survival benefit which has led to an update in the current treatment guidelines of RCC. This substantial change in the standard of care also caused an investigation of possible treatment combinations and an adoption of innovative predictive biomarkers. In this review, we will present the evolution of past adjuvant ICI trials for the treatment of RCC, the implications of pembrolizumab's overall survival benefits and a discussion of future directions concerning new RCC drug trials and liquid biopsy-based biomarkers.
近年来,全球范围内肾癌的发病率呈上升趋势,每年新增病例超过 40 万。尽管超过一半的患者在局部阶段被诊断出来,但这种疾病在手术后仍有很高的复发风险。因此,需要在手术后进行辅助治疗,以降低癌症复发率,延长无病生存期和总生存期。在过去的五十年中,对肾细胞癌(RCC)的辅助药物进行了彻底的研究,但没有发现总体生存获益。直到免疫检查点抑制剂 pembrolizumab 通过 KEYNOTE-564 试验被引入辅助 RCC 领域,这种情况才有所改变。这种新型抗 PD-1 药物的辅助给药显著提高了总体生存率,这导致了 RCC 治疗指南的更新。这种对治疗标准的重大改变也促使人们对可能的治疗组合进行了调查,并采用了创新的预测生物标志物。在这篇综述中,我们将介绍过去用于治疗 RCC 的辅助 ICI 试验的发展,讨论 pembrolizumab 带来的总体生存获益,以及探讨新的 RCC 药物试验和基于液体活检的生物标志物的未来方向。