Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

Park, Chan Su; Sung, Min Je; Kim, So Jeong; Jo, Jung Hyun; Lee, Hee-Seung; Chung, Moon Jae; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Park, Jeong Youp

doi:10.3390/cancers14174323

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…In our study, MSI-H status was a protective factor for both OS and PFS of immunotherapy in multivariate analysis. However, another study found that MSI-H ( N = 15) was not an independent protective factor ( P = 0.162) in refractory CCA with PD-L1 positivity (CPS≥ 1 or tumor proportion score (TPS) ≥ 1%) and treated with pembrolizumab, indicating that PD-L1 expression is also another important confounding factor [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma

Yang,

Lian,

Zhang

et al. 2024

BMC Med

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Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy. Conclusions MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS. Trial registration This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).

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Section: Discussionmentioning

confidence: 99%

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma

Yang,

Lian,

Zhang

et al. 2024

BMC Med

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“…Hyerim Ha1 et al [ 26 ] found that patients with high levels of NLR, PLR, and SII had poorer OS by analyzing the hematological indicators of 158 patients with advanced BTC. Chan Su Park et al [ 27 ] also found in a retrospective study that lower MLR was significantly associated with better OS in patients with advanced BTC treated with pembrolizumab in the second line. This result is consistent with the results in the retrospective study we conducted, in which we also found a significant correlation between lower NLR ( p = 0.0083), PLR ( p = 0.020), SII ( p = 0.0161), and MLR ( p < 0.001) and better OS of patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effectiveness of chemotherapy combined with immunotherapy and chemotherapy alone in advanced biliary tract cancer and construction of the nomogram for survival prediction based on the inflammatory index and controlling nutritional status score

Zhang,

Wang,

Zhang

et al. 2023

Cancer Immunol Immunother

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Objective To analyze the effectiveness of combining immune checkpoint inhibitors (ICIs) with first-line therapy in patients with advanced biliary tract cancer (BTC) and explore the biomarkers affecting the prognosis of immunotherapy, to construct a nomogram for the prediction of survival. Methods A retrospective study was conducted to include a total of 209 patients with advanced BTC treated in the first line from 2018 to 2022, divided into a combination therapy group (n = 129) and a chemotherapy-only group (n = 80) according to whether ICIs were applied in combination. Univariate and multifactorial COX regression analyses were performed on variables that may affect prognosis to identify independent influences on patient prognosis, and this was used to create nomograms, which were then prospectively validated and calibrated. Results The median progression-free survival (mPFS) and median overall survival (mOS) of patients in the combination therapy group were higher than those in the chemotherapy alone group [hazard ratio (HR) = 1.152, 95% confidence interval (CI): 0.7848–1.692, p = 0.0004, and HR = 1.067, 95% CI: 0.7474–1.524, p = 0.0016]. The objective response rate (ORR) of patients in the combination therapy and chemotherapy alone groups was 39.5% (51/129) vs. 27.5% (22/80), and the disease control rate (DCR) between the two groups was 89.9% (116/129) vs. 83.8% (67/80). Univariate analysis revealed the gender, presence of long-term tobacco and alcohol, degree of histological differentiation, serum albumin level, presence of liver metastases, presence of multi-visceral metastases, response, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), glycoprotein antigen 19-9 (CA19-9), systemic inflammatory index (SII), and controlling nutritional status (CONUT) scores were statistically significant with patient prognosis (all P values < 0.05). Multi-factor COX regression analysis was continued for the above variables, and the results showed that NLR, MLR, PLR, SII, and CONUT scores were independent influences on patients’ OS (all p values < 0.05). A nomogram (C-index 0.77, 95% CI: 0.71–0.84) was created based on these independent influences and later validated using a validation cohort (C-index 0.75, 95% CI: 0.68–0.81). The time-dependent receiver operator characteristic curve (ROC) showed that the area under curve (AUC) of the training cohort patients at 12, 18, and 24 months was 0.72 (95% CI: 0.63–0.81), 0.75 (95% CI: 0.67–0.85), and 0.77 (95% CI: 0.66–0.87) and the AUC of the validation cohort was 0.69 (95% CI: 0.58–0.79), 0.74 (95% CI: 0.65–0.87), and 0.71 (95% CI: 0.64–0.89), respectively. Finally, calibration was performed using calibration curves, and the results showed that nomograms based on inflammatory metrics and CONUT scores could be used to assess survival (12, 18, and 24 months) in patients with advanced BTC treated with ICIs in the first line. Conclusion Patients with advanced BTC benefit more from first-line treatment with standard chemotherapy in combination with ICIs than with chemotherapy alone. In addition, nomograms based on inflammatory metrics and CONUT scores can be used to predict survival at 12, 18, and 24 months in patients with advanced BTC treated with ICIs.

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Recent updates in the therapeutic uses of Pembrolizumab: a brief narrative review

Silva,

Matos

2024

Clin Transl Oncol

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Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

Cited by 5 publications

References 27 publications

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma

Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma

Comparison of the effectiveness of chemotherapy combined with immunotherapy and chemotherapy alone in advanced biliary tract cancer and construction of the nomogram for survival prediction based on the inflammatory index and controlling nutritional status score

Recent updates in the therapeutic uses of Pembrolizumab: a brief narrative review

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