The MAGIC-D Prognostic Score: Another Small Step in the Direction of Precision Oncology in Advanced Biliary Tract Cancer

IF 5.2 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Octave Letissier, Julien Edeline
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With this new standard of care, it is important to refine our prognostication of patients, as there are no widely accepted prognostic classifications of advanced BTC. A better prognostication might help us to more precisely personalise treatment.</p><p>Persona and colleagues made a huge effort by pooling a large multicentre global database of 618 patients treated with this new regimen. They developed a simple prognostic score, showing independent prognostic value of widely available variables (metastatic disease, carcinoembryonic antigen, albumin, gamma-glutamyl transferase, neutrophils-to-lymphocyte ratio), combining them in a score which was able to classify patients in 3 groups with clearly different outcomes (median OS and progression-free survival (PFS) of 18.4 and 11.7 in low-risk, 15.9 and 8.7 in intermediate-risk, and 7.8 and 5.4 months in high-risk groups, respectively). 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The work has also some limitations: the follow-up was quite short, less than 1 year, and the evaluation of long-term survival might be less precise, especially taking into account that the benefit of immunotherapy is maintained at long term; the authors pooled together perihilar cholangiocarcinoma, distal cholangiocarcinoma and gallbladder carcinoma in an “other primary sites” category, while each of them might have differences in prognosis, gallbladder cancer having potentially a worse prognosis [<span>6</span>]; only 319 patients who had all variables available were included in the final multivariable model and 79 patients in the validation cohort; there was no molecular data available, while some data suggest differences in prognosis depending on molecular alterations [<span>7, 8</span>].</p><p>Overall, this score might be useful for better defining prognosis on the current standard of care. 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Strong international collaborations such as this presented by Persona and colleagues are the only way to achieve this goal in this rare cancer!</p><p>O.L. declare no conflicts of interest. J.E. declares Consulting: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene, Taiho, Boston Scientific, Guerbet, Jazz, Captor therapeutics; Research funding (institutional): BMS, Beigene, Boston Scientific, Exeliom biosciences, SUMMIT, AstraZeneca.</p><p>This article is linked to Persano et al. paper. 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引用次数: 0

Abstract

In this issue of Liver International, Persona et al. defined and validated a new prognostic score for advanced biliary tract cancer (BTC) treated with the current first-line standard of care, cisplatin-gemcitabine-durvalumab, the MAGIC-D score [1]. The addition of immunotherapy to chemotherapy has been shown to improve Overall Survival (OS) over chemotherapy alone in two large phase 3 trials, with durvalumab in the TOPAZ-1 trial, or with pembrolizumab in the KEYNOTE-966 trial [2, 3]. While the improvement could be seen as modest at the median, it is confirmed as persisting at long-term follow-up, and was able to preserve quality-of-life [4, 5]. With this new standard of care, it is important to refine our prognostication of patients, as there are no widely accepted prognostic classifications of advanced BTC. A better prognostication might help us to more precisely personalise treatment.

Persona and colleagues made a huge effort by pooling a large multicentre global database of 618 patients treated with this new regimen. They developed a simple prognostic score, showing independent prognostic value of widely available variables (metastatic disease, carcinoembryonic antigen, albumin, gamma-glutamyl transferase, neutrophils-to-lymphocyte ratio), combining them in a score which was able to classify patients in 3 groups with clearly different outcomes (median OS and progression-free survival (PFS) of 18.4 and 11.7 in low-risk, 15.9 and 8.7 in intermediate-risk, and 7.8 and 5.4 months in high-risk groups, respectively). This was validated in a small confirmatory cohort (n = 79, median OS and PFS of not reached and 12.8 months in the low-risk, 19.6 and 8.5 months in the intermediate-risk, and 12.2 and 5.0 in the high-risk groups, respectively).

This work has several strengths: it was developed in a large series, with patients from different regions of the globe, improving generalizability of the results; the use of real-world data is important because the patients included are less selected than in prospective clinical trials; the score is very simple, easy to calculate and despite this can provide important prognostic information. The work has also some limitations: the follow-up was quite short, less than 1 year, and the evaluation of long-term survival might be less precise, especially taking into account that the benefit of immunotherapy is maintained at long term; the authors pooled together perihilar cholangiocarcinoma, distal cholangiocarcinoma and gallbladder carcinoma in an “other primary sites” category, while each of them might have differences in prognosis, gallbladder cancer having potentially a worse prognosis [6]; only 319 patients who had all variables available were included in the final multivariable model and 79 patients in the validation cohort; there was no molecular data available, while some data suggest differences in prognosis depending on molecular alterations [7, 8].

Overall, this score might be useful for better defining prognosis on the current standard of care. This score, if validated independently, could certainly be used for stratification in clinical trials, as it might provide three groups with clear different outcomes. The parameters are objective, while performance status is currently frequently used but is, however, quite subjective. The better stratification might also be used for discussion with patients regarding their potential outcomes: in a disease with an overall grim prognosis, having more precise information about prognosis might help to more adequately respond to patients' queries about their future.

Importantly, this score could not currently be used for selection of treatment, especially for the use or not of immunotherapy. Indeed, there was no control group to show that the differences in survival are specific to durvalumab. In contrast, it is very likely that the score is prognostic rather than predictive. Durvalumab might also have improved outcomes in the high-risk group, which still showed in the validation cohort a quite high median OS.

How could we improve prognostication of advanced BTC over the MAGIC-D score? The incorporation of molecular data is likely to be used in the future not only for selection of targeted therapy use, but also for prognostication. But more importantly, it would be of major importance to develop biomarkers for prediction of benefit from chemotherapy, immunotherapy, or both. Precision oncology is already a reality for the treatment of BTC, with the use of targeted therapy as second-line treatment [9]. While the inclusion of molecular therapy in the first-line setting might be an important avenue of research [10], the better selection of chemotherapy and immunotherapy might have broader implications, whatever the targeted alterations present in the tumour. Strong international collaborations such as this presented by Persona and colleagues are the only way to achieve this goal in this rare cancer!

O.L. declare no conflicts of interest. J.E. declares Consulting: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene, Taiho, Boston Scientific, Guerbet, Jazz, Captor therapeutics; Research funding (institutional): BMS, Beigene, Boston Scientific, Exeliom biosciences, SUMMIT, AstraZeneca.

This article is linked to Persano et al. paper. To view this article, visit https://doi.org/10.1111/liv.70181.

MAGIC-D预后评分:晚期胆道癌精准肿瘤治疗的又一小步
在本期《肝脏国际》杂志上,Persona等人定义并验证了采用当前一线治疗标准顺铂-吉西他滨-杜伐单抗治疗的晚期胆道癌(BTC)的新的预后评分,MAGIC-D评分为[1]。在两项大型3期试验中,在化疗中加入免疫治疗已被证明比单独化疗更能提高总生存期(OS), TOPAZ-1试验中使用durvalumab, KEYNOTE-966试验中使用pembrolizumab[2,3]。虽然这种改善在中位数上是温和的,但在长期随访中被证实是持续的,并且能够保持生活质量[4,5]。有了这个新的护理标准,完善我们对患者的预测是很重要的,因为目前还没有广泛接受的晚期BTC的预后分类。更好的预测可能会帮助我们更精确地进行个性化治疗。Persona及其同事做出了巨大的努力,汇集了618名接受这种新方案治疗的患者的大型多中心全球数据库。他们开发了一个简单的预后评分,显示了广泛可用的变量(转移性疾病、癌胚抗原、白蛋白、γ -谷氨酰转移酶、中性粒细胞与淋巴细胞比率)的独立预后价值,并将它们合并成一个评分,能够将具有明显不同结果的3组患者分类(低危组中位OS和无进展生存期(PFS)分别为18.4和11.7个月,中危组为15.9和8.7个月,高危组为7.8和5.4个月)。分别)。在一个小型验证队列中验证了这一点(n = 79,中位OS和PFS未达到,低危组为12.8个月,中危组为19.6个月和8.5个月,高危组为12.2和5.0个月)。这项工作有几个优势:它是在一个大系列中开发的,患者来自全球不同地区,提高了结果的普遍性;使用真实数据很重要,因为纳入的患者比前瞻性临床试验中选择的少;该评分非常简单,易于计算,尽管如此,仍可提供重要的预后信息。这项工作也有一些局限性:随访时间很短,不到1年,长期生存的评估可能不太精确,特别是考虑到免疫治疗的益处是长期维持的;作者将肝门周围胆管癌、远端胆管癌和胆囊癌归为“其他原发部位”一类,而每一种胆囊癌的预后可能存在差异,胆囊癌的预后可能更差;最终的多变量模型中只有319例患者具有所有可用变量,验证队列中只有79例患者;没有分子数据,而一些数据表明预后差异取决于分子改变[7,8]。总的来说,该评分可能有助于更好地确定当前护理标准的预后。如果独立验证,该评分当然可以用于临床试验中的分层,因为它可能提供三组明显不同的结果。这些参数是客观的,而目前经常使用的性能状态是相当主观的。更好的分层还可以用于与患者讨论其潜在结果:在总体预后不佳的疾病中,掌握更准确的预后信息可能有助于更充分地回答患者对其未来的询问。重要的是,这个评分目前还不能用于治疗的选择,尤其是是否使用免疫治疗。事实上,没有对照组表明durvalumab的生存差异是特异性的。相反,这个分数很可能是预示性的,而不是预测性的。Durvalumab在高风险组中也可能有改善的结果,在验证队列中仍然显示出相当高的中位OS。与MAGIC-D评分相比,我们如何改善晚期BTC的预测?结合分子数据可能在未来不仅用于靶向治疗的选择,而且用于预后。但更重要的是,开发生物标志物来预测化疗、免疫治疗或两者的益处将是非常重要的。精准肿瘤学治疗BTC已经成为现实,靶向治疗作为二线治疗[9]。虽然在一线环境中纳入分子治疗可能是一个重要的研究途径,但更好地选择化疗和免疫治疗可能具有更广泛的意义,无论肿瘤中存在何种靶向改变。像Persona及其同事所提出的这样强有力的国际合作是在这种罕见的癌症中实现这一目标的唯一途径声明没有利益冲突。J.E. 声明咨询:默沙东、卫材、BMS、阿斯利康、拜耳、罗氏、易普生、巴赛利亚、默克雪兰诺、Incyte、施维雅、百济神州、Taiho、Boston Scientific、Guerbet、Jazz、Captor therapeutics;研究资助(机构):BMS,百济神州,波士顿科学,Exeliom生物科学,SUMMIT,阿斯利康。这篇文章链接到Persano等人的论文。要查看本文,请访问https://doi.org/10.1111/liv.70181。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Liver International
Liver International 医学-胃肠肝病学
CiteScore
13.90
自引率
4.50%
发文量
348
审稿时长
2 months
期刊介绍: Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.
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