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. 2022 Nov;127(9):1701-1708.
doi: 10.1038/s41416-022-01932-1. Epub 2022 Aug 19.

Precision oncology for intrahepatic cholangiocarcinoma in clinical practice

Aurelie Tomczak  1   2 , Christoph Springfeld  2   3 , Michael T Dill  2   4   5 , De-Hua Chang  2   6 , Daniel Kazdal  1 , Ursula Wagner  1   2   3 , Arianeb Mehrabi  2   7 , Antje Brockschmidt  2   8 , Tom Luedde  9 , Patrick Naumann  2   10 , Albrecht Stenzinger  1 , Peter Schirmacher  1   2 , Thomas Longerich  11   12
Affiliations

Precision oncology for intrahepatic cholangiocarcinoma in clinical practice

Aurelie Tomczak et al. Br J Cancer. 2022 Nov.

Abstract

Background: Advanced cholangiocarcinoma has a poor prognosis. Molecular targeted approaches have been proposed for patients after progression under first-line chemotherapy treatment. Here, molecular profiling of intrahepatic cholangiocarcinoma in combination with a comprehensive umbrella concept was applied in a real-world setting.

Methods: In total, 101 patients received molecular profiling and matched treatment based on interdisciplinary tumour board decisions in a tertiary care setting. Parallel DNA and RNA sequencing of formalin-fixed paraffin-embedded tumour tissue was performed using large panels.

Results: Genetic alterations were detected in 77% of patients and included gene fusions in 21 patients. The latter recurrently involved the FGFR2 and the NRG1 gene loci. The most commonly altered genes were BAP1, ARID1A, FGFR2, IDH1, CDKN2A, CDKN2B, PIK3CA, TP53, ATM, IDH2, BRAF, SMARCA4 and FGFR3. Molecular targets were detected in 59% of patients. Of these, 32% received targeted therapy. The most relevant reason for not initiating therapy was the deterioration of performance status. Patients receiving a molecular-matched therapy showed a significantly higher survival probability compared to patients receiving conventional chemotherapy only (HR: 2.059, 95% CI: 0.9817-4.320, P < 0.01).

Conclusions: Molecular profiling can be successfully translated into clinical treatment of intrahepatic cholangiocarcinoma patients and is associated with prolonged survival of patients receiving a molecular-matched treatment.

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Conflict of interest statement

AT, DC, UW, AM, AB and PN declare no potential conflicts of interest that pertain to this work. CS reports honoraria for advisory boards from Roche, MSD, Bayer, Servier, AstraZeneca and Eisai outside the submitted work. MTD declares speaker and advisory board activities for AstraZeneca, Eisai and Roche outside the submitted work. DK declares personal fees from Agilent, AstraZeneca, Bristol-Myers Squibb, Lilly, Pfizer, and Takeda outside the submitted work. TLu declares research support and/or speaker´s honoraria from AstraZeneca, Bayer, BMS, EASL, Incyte, MSD and Roche. AS declares speakers´ bureau and advisory board activities by AGCT, Aignostics, Amgen, AstraZeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda and Thermo Fisher as well as grant support by Bayer, BMS, Chugai, and Incyte. PS declares speakers´ bureau activities for BMS, Incyte, Eisai, Leica, Janssen, Novartis, advisory board activities for AstraZeneca, Bayer, BMS, Eisai, Incyte, MSD and Roche as well as grant support from BMS, Chugai, Incyte, MSD and Roche outside the submitted work. TLo declares the speaker´s honorarium by Incyte.

Figures

Fig. 1
Fig. 1. Most prevalent genomic alterations detected among patients with intrahepatic cholangiocarcinoma (n = 101).
The given frequencies were calculated based on the number of patients with both available DNA and RNA sequencing data (n = 74). The type of alteration is colour-coded.
Fig. 2
Fig. 2. Efficacy of translating molecular profiling into patient’s treatment.
The pie chart details the frequencies and reasons for receiving or not receiving a molecular-matched therapy.
Fig. 3
Fig. 3. Flowchart of the patients sequenced within the LCCH umbrella.
Finally, a molecular target was available in 38 out of 47 patients, from which 19 received a molecular-matched drug treatment.
Fig. 4
Fig. 4. Impact of targeted treatment on overall survival.
Kaplan–Meier curve of overall survival in patient’s receiving a molecular targeting drug compared to patients receiving standard treatment. The patients remaining at risk are detailed below the diagram. HR hazard ratio, CI confidence interval.
See this image and copyright information in PMC

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