A Prognostic Index for Advanced Biliary Tract Cancer Treated With Cisplatin, Gemcitabine and Durvalumab: The MAGIC-D Index.

Background: Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first-line setting.

Patients And Methods: The study population consisted of patients with BTC from 11 Eastern and Western Countries. Using multivariate analysis for overall survival (OS), we identified 5 baseline statistically significant variables: stage, carcinoembryonic antigen (CEA) levels, albumin levels, gamma glutamyl transferase (GGT) levels, neutrophil-to-lymphocyte ratio (NLR). Metastatic disease is a prognostic factor with a superior weight considering the HR of 3.62, while all the others can be considered prognostic factors with equivalent weight as the HRs are quite similar (HRs between 1.55 and 1.92). Based on these reasons, we developed a prognostic model called the MAGIC-D index by assigning a score of 2 for metastatic disease, and a score of 1 for CEA increased levels, albumin decreased levels, GGT increased levels, NLR ≥ 3. Patients were stratified into three risk groups as follows: low-risk group (Score from 0 to 2), intermediate-risk group (Score from 3 to 4) and high-risk group (Score from 5 to 6). At the first data cutoff (April 2024), these data were available for 319 patients that composed the training cohort used for the analysis. At the second data cutoff (May 2025), 79 patients were further enrolled and composed the validation cohort.

Results: Median progression-free survival was 11.7 months in low-risk group (20.7%), 8.7 months in intermediate-risk group (46.4%) and 5.4 months in high-risk group (32.9%) [low-risk hazard ratio (HR): 0.27, intermediate-risk HR: 0.55, high-risk HR: 1, p < 0.0001]. Median OS was 18.4 months in low-risk group,15.9 months in intermediate-risk group and 7.8 months in high-risk group (low-risk HR: 0.17, intermediate-risk HR: 0.43, high-risk HR: 1, p < 0.0001). There was no difference in overall response rate (low-risk: 31.8%, intermediate-risk: 36.5% and high-risk: 25.7%; p = 0.0718), while disease control rate was significantly different across the three risk groups (low-risk: 83.3%, intermediate-risk: 70.9% and high-risk: 60.9%; p < 0.0001) as well as the rate of patients receiving a second-line therapy (low-risk: 54.5%, intermediate-risk: 48.6% and high-risk: 25.7%; p = 0.0061). Finally, the prognostic role in terms of OS and PFS of the MAGIC-D index was confirmed in a validation cohort of 79 patients.

Conclusion: The MAGIC-D index is an easy-to-use tool able to stratify patients with BTC with different prognoses undergoing first-line therapy with CGD.