Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology.
Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology.
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免疫检查点抑制剂（ICIs）在早期肿瘤的初步治疗后被越来越多地使用，以治疗任何残留疾病并预防复发。在此，我们对关键临床研究进行了全面综述，这些研究证明了在黑色素瘤、尿路上皮癌、肾细胞癌、肺癌、胃食管癌和肝胆恶性肿瘤患者术后使用 ICI 的有效性和安全性结果。此外，我们强调这些药物在新兴的移植肿瘤学领域的潜在作用。为了指导选择符合 ICI 的患者，我们概述了已批准的和新兴的生物标志物，这些生物标志物可以预测使用这些药物的益处并帮助监测反应，特别是在影像学上没有明显疾病的情况下。此外，我们提供了有关这些药物的耐受性和成本效益的现实考虑因素，以及应探索的必要的未来方向，以提高与术后使用 ICI 相关的生存结果。在辅助治疗中使用免疫检查点抑制剂（ICIs）的基本原理是根除微转移，并最终延长生存期。迄今为止，临床试验已证明 ICI 的 1 年辅助疗程可降低黑色素瘤、尿路上皮癌、肾细胞癌、非小细胞肺癌以及食管癌和胃食管交界癌的复发风险。黑色素瘤的总体生存获益已得到证实，而其他恶性肿瘤的生存数据尚未成熟。新数据还显示了在肝胆恶性肿瘤移植围手术期使用 ICI 的可行性。虽然 ICI 通常耐受性良好，但慢性免疫相关不良事件（通常是内分泌疾病或神经毒性）以及迟发性免疫相关不良事件的发生，需要进一步审查辅助治疗的最佳持续时间，并需要彻底的风险效益确定。基于血液的动态生物标志物（例如循环肿瘤 DNA (ctDNA)）的出现可以帮助检测微小残留疾病，并确定可能从辅助治疗中受益的患者子集。此外，肿瘤浸润淋巴细胞、中性粒细胞与淋巴细胞比率和 ctDNA 调整的血液肿瘤突变负荷 (bTMB) 的特征也显示出在预测免疫治疗反应方面的前景。在更多的前瞻性研究描绘出总体生存获益的程度并验证预测性生物标志物的使用之前，应将一种量身定制的、以患者为中心的辅助 ICI 方法（包括针对潜在不可逆不良反应的广泛患者咨询）纳入临床实践。
Immune checkpoint inhibitors (ICIs) are being increasingly used after primary treatment of early-stage tumors to treat any residual disease and prevent recurrence. Herein, we provide a comprehensive review of pivotal clinical studies demonstrating efficacy and safety outcomes when ICIs are utilized after surgery in patients with melanoma, urothelial cancer, renal cell carcinoma, lung cancer, gastroesophageal cancer, and hepatobiliary malignancies. In addition, we highlight the potential role of these agents within the emerging field of transplant oncology. To guide the selection of eligible patients for ICIs, we outline approved and emerging biomarkers that may predict benefit from use of these agents and help monitor response, especially in the absence of visible disease on imaging. Furthermore, we provide real-world considerations with regards to tolerability and cost-effectiveness of these agents and necessary future directions that should be explored to increase the survival outcomes associated with the use of ICIs after surgery. The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk–benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.
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DOI：
10.7759/cureus.11150
发表时间：
2020-10-25
期刊：
Cureus
影响因子：
--
作者：
Al Jarroudi O;Ulusakarya A;Almohamad W;Afqir S;Morere JF
通讯作者：
Morere JF
影响因子：
2
作者：
Au KP;Chok KSH
通讯作者：
Chok KSH
影响因子：
8.4
作者：
Ameratunga, Malaka;Chenard-Poirier, Maxime;Lopez, Juanita
通讯作者：
Lopez, Juanita
影响因子：
4.7
作者：
Abdelrahim, Maen;Esmail, Abdullah;Xu, Jiaqiong;Umoru, Godsfavour;Al-Rawi, Hadeel;Saharia, Ashish;Abudayyeh, Ala;Victor, David;McMillan, Robert;Kodali, Sudha;Ghobrial, Rafik M.
通讯作者：
Ghobrial, Rafik M.
DOI：
10.1016/j.jceh.2019.11.009
发表时间：
2020-03-01
影响因子：
3
作者：
Amjad, Waseem;Kotiah, Sandy;Thuluvath, Paul J.
通讯作者：
Thuluvath, Paul J.