{"title":"The MAGIC-D Prognostic Score: Another Small Step in the Direction of Precision Oncology in Advanced Biliary Tract Cancer","authors":"Octave Letissier, Julien Edeline","doi":"10.1111/liv.70243","DOIUrl":null,"url":null,"abstract":"<p>In this issue of <i>Liver International</i>, 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 [<span>1</span>]. 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 [<span>2, 3</span>]. 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 [<span>4, 5</span>]. 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). This was validated in a small confirmatory cohort (<i>n</i> = 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).</p><p>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 [<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. 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.</p><p>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.</p><p>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 [<span>9</span>]. While the inclusion of molecular therapy in the first-line setting might be an important avenue of research [<span>10</span>], 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!</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. To view this article, visit https://doi.org/10.1111/liv.70181.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70243","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver International","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/liv.70243","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
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.
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.