Advances in the systemic treatment of therapeutic approaches in biliary tract cancer

Landolfi, Stefania; López-Valbuena, D.; García-Illescas, David; Fabregat-Franco, Carles; Verdaguer, Helena; Tabernero, Josep; Macarulla, Teresa

doi:10.1016/j.esmoop.2022.100503

Cited by 13 publications

(8 citation statements)

References 100 publications

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“…As a result, they found that the ORR of dual immunotherapy combination was even 2% lower than that of single-agent immunotherapy combination; therefore, they concluded that chemotherapy combined with dual immunotherapy did not show significant advantages over single-agent immunotherapy in the first-line treatment of patients with advanced BTC, and even increased the financial cost for patients compared to single-agent immunotherapy. The study also found that the ORR of patients treated with second-line therapy in combination with immunotherapy was 20% lower than that of patients treated with first-line therapy, suggesting that patients benefit more from the combination of ICIs at first-line therapy in the treatment of patients with advanced BTC, This result is consistent with both our retrospective study and the results of the phase III clinical trial of TOPAZ-1 [ 7 , 19 , 23 ].…”

Section: Discussionsupporting

confidence: 88%

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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Section: Discussionsupporting

confidence: 88%

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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“…Tyrosine kinase receptors known as FGFRs are implicated in regulating RAS, Janus kinase 2, and phosphoi-nositide 3-kinases (PI3K)/mammalian target of rapamycin pathways, and FGFR2 abnormalities affect cellular migration, angiogenesis, proliferation, and survival processes[ 38 , 39 ]. Numerous medications that target FGFR isoforms, including infigratinib, pemigatinib, derazantinib, erdafitinib (ATP-competitive, reversible inhibitors), and futibatinib (non-ATP-competitive, covalent inhibitor), have been studied in iCCA patients during the past ten years[ 40 , 41 ]. In a phase 1 clinical trial with 3 CCA patients carrying FGFR2 abnormalities, the pan-FGFR tyrosine kinase inhibitor infigratinib was originally evaluated, and all patients had stable condition[ 42 ].…”

Section: Targeted Therapiesmentioning

confidence: 99%

Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer

Leowattana¹,

Leowattana²,

Leowattana³

2023

World J Gastrointest Oncol

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Biliary tract cancers (BTC) are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens. For more than a decade, the combination of gemcitabine and cis-platin has served as the first-line standard treatment. There are few choices for second-line chemo-therapy. Targeted treatment with fibroblast growth factor receptor 2 inhibitors, neurotrophic tyrosine receptor kinase inhibitors, and isocitrate dehydrogenase 1 inhibitors has had important results. Immune checkpoint inhibitors (ICI) such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients. The TOPAZ-1 trial's outcome is encouraging, and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options. Newer targets and agents for existing goals are being studied, which may represent a paradigm shift in BTC management. Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications, the new category of drugs may occupy a significant role in BTC therapies.

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“… 3 Over the last 10 years, the prognosis of patients has changed significantly, mainly due to the availability of systemic treatment, both adjuvant and, in particular, systemic treatment of metastatic disease with targeted drugs. 3 , 4 , 7 , 8 …”

Section: Introductionmentioning

confidence: 99%

Determination of copper and other trace elements in serum samples from patients with biliary tract cancers: prospective noninterventional nonrandomized clinical study protocol

Rebersek,

Hribernik,

Markovic

et al. 2024

Radiology and Oncology

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Background Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS). Patients and methods In this prospective, noninterventional, nonrandomized study 20 patients and 20 healthy volunteers will be enrolled to identify serum Cu, Zn and Fe levels, Cu isotopic fractionation as a predictive biomarker of response to systemic therapy of BTCs, which will be evaluated by computed tomography. Newly developed analytical methods based on ICP-MS will be applied to metal-based biomarker research in oncology. Conclusions In the study the comparison of the total concentration of selected trace elements, the proportion of free Cu and Cu bound to Cp and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients will be conducted to provide the foundation for the development of a BTC cancer screening methodology and the data on their usability as a potential predictive biomarker for BTCs of response to systemic therapy.

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Advances in the systemic treatment of therapeutic approaches in biliary tract cancer

Cited by 13 publications

References 100 publications

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

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

Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer

Determination of copper and other trace elements in serum samples from patients with biliary tract cancers: prospective noninterventional nonrandomized clinical study protocol

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