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Real-World Data on Ivosidenib in Patients with Previously Treated Isocitrate Dehydrogenase 1-Mutated Intrahepatic Cholangiocarcinomas: An Early Exploratory Analysis

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Abstract

Background

The results of the phase III ClarIDHy trial have led to US FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations.

Objective

In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib.

Patients and Methods

Patients treated with ivosidenib as second and third line for advanced CCA were collected with the aim of evaluating the survival outcomes. A molecular study has been performed by next-generation sequencing assay.

Results

After a median follow up of 9.4 months, median progression-free survival (PFS) from the start of treatment with ivosidenib was 4.4 months (95% confidence interval [CI] 3.3–5.8), whereas median overall survival (OS) was not reached. The disease control rate was 62.5%, with two patients achieving a partial response (25%); 12.5% of patients experienced a treatment-related adverse event (AE), but no grade 3 or higher AEs were reported. The observed grade 2 AEs were prolonged QT interval and hypomagnesemia (25% of the sample). Molecular profiling was performed on six of eight patients, highlighting TP53, BAP1, CDKN2A and CDKN2B as the most common co-altered genes in these patients.

Conclusion

Efficacy outcomes were consistent with those reported in the ClarIDHy trial. Real-world experiences on larger samples are needed in order to confirm our results.

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Author information

Authors and Affiliations

  1. Department of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy

    Margherita Rimini & Valentina Burgio

  2. Clinical Oncology Unit, Careggi University Hospital, Florence, Italy

    Lorenzo Antonuzzo & Daniele Lavacchi

  3. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Lorenzo Antonuzzo

  4. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Lorenza Rimassa

  5. Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy

    Lorenza Rimassa & Nicola Personeni

  6. Oncology Department, Poliambulanza Hospital of Brescia, Brescia, Italy

    Ester Oneda

  7. Hepatobiliary Surgery Department, IRCCS San Raffaele Hospital, Milan, Italy

    Francesca Ratti & Luca Aldrighetti

  8. Department of Pathology, San Raffaele Scientific Institute, Milan, Italy

    Federica Pedica

  9. Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy

    Angelo Della Corte

  10. Oncology Department, University Hospital of Cagliari, Cagliari, Italy

    Mara Persano & Mario Scartozzi

  11. Vita-Salute University San Raffaele, Milan, Italy

    Francesco De Cobelli, Stefano Cascinu & Andrea Casadei-Gardini

Authors
  1. Margherita Rimini
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  2. Valentina Burgio
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  3. Lorenzo Antonuzzo
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  4. Lorenza Rimassa
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  5. Ester Oneda
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  6. Daniele Lavacchi
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  7. Nicola Personeni
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  8. Francesca Ratti
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  9. Federica Pedica
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  10. Angelo Della Corte
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  11. Mara Persano
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  12. Francesco De Cobelli
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  13. Luca Aldrighetti
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  14. Mario Scartozzi
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  15. Stefano Cascinu
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  16. Andrea Casadei-Gardini
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Corresponding author

Correspondence to Margherita Rimini.

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Funding

No external funding was used in the preparation of this manuscript.

Conflicts of interest/Competing interests

Nicola Personeni has received consulting fees from Amgen, Merck Serono, and Servier; lectures fees from AbbVie, Gilead, Lilly, and Sanofi; travel expenses from Amgen and ArQule; and institutional research funding from Basilea, Merck Serono, and Servier. Lorenza Rimassa has received consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Taiho Oncology, and Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, and Sanofi; travel expenses from AstraZeneca; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. Margherita Rimini, Valentina Burgio, Lorenzo Antonuzzo, Ester Oneda, Daniele Lavacchi, Francesca Ratti, Federica Pedica, Angelo Della Corte, Mara Persano, Francesco De Cobelli, Luca Aldrighetti, Mario Scartozzi, Stefano Cascinu, and Andrea Casadei-Gardini declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

The Ethical Review Board of each institutional hospital approved the present study. This study was performed in line with the principles of the Declaration of Helsinki.

Consent to participate

Patients provided informed consent for treatment with ivosidenib, which is not yet approved in Italy. Under the conditions of retrospective archival tissue collection and anonymization of patients’ data, our study was exempted from the acquisition of informed consent for retrospective data analysis from patients, by the Institutional Review Board.

Consent for publication

Not applicable.

Availability of data and material

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Authors' contributions

Study conception and design: MR, AC-G. Acquisition of data (acquired and managed patients): All authors. Analysis and interpretation of data: MR, AC-G. Writing, review, and/or revision of the manuscript: All authors. Final approval of the manuscript: All authors.

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Cite this article

Rimini, M., Burgio, V., Antonuzzo, L. et al. Real-World Data on Ivosidenib in Patients with Previously Treated Isocitrate Dehydrogenase 1-Mutated Intrahepatic Cholangiocarcinomas: An Early Exploratory Analysis. Targ Oncol 17, 591–596 (2022). https://doi.org/10.1007/s11523-022-00917-7

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  • DOI: https://doi.org/10.1007/s11523-022-00917-7

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