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Clinical Studies

A randomised phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumours

British Journal of Cancer volume 129, pages 275–282 (2023)Cite this article

Subjects

Abstract

Background

Imatinib re-challenge is one of the available therapeutic options for patients with treatment-refractory gastrointestinal stromal tumours (GIST). Intermittent dosing of imatinib was suggested to delay outgrow of the imatinib-resistant clones in a preclinical study, and it could potentially reduce the adverse events.

Methods

A randomised phase 2 study was performed to evaluate the efficacy and safety of a continuous or intermittent imatinib schedule in GIST patients whose disease had progressed to at least imatinib and sunitinib.

Results

Fifty patients were included in the full analysis set. The disease control rate at 12 weeks was 34.8% and 43.5%, and median progression-free survival was 1.68 and 1.57 months in the continuous and intermittent groups, respectively. The frequency of diarrhoea, anorexia, decreased neutrophil, or dysphagia was lower in the intermittent group. The scores for global health status/quality of life was not significantly deteriorated over the 8 weeks in both groups.

Conclusions

The intermittent dosage did not improve the efficacy outcomes as compared to the continuous dosage, but showed slightly better safety profiles. Given the limited efficacy of imatinib re-challenge, intermittent dosage may also be considered in clinical circumstances where standard fourth-line agent is unavailable or all other viable treatments failed.

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Fig. 1: Survival outcomes of patients in the continous and intermittent groups.
Fig. 2

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Data availability

Not applicable.

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Acknowledgements

The study drug was supplied by HK inno.N Corp. This study was presented in part at the ASCO Annual Meeting 2022.

Funding

None.

Author information

Author notes

  1. These authors contributed equally: Hyung-Don Kim, Changhoon Yoo.

Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Hyung-Don Kim, Changhoon Yoo, Min-Hee Ryu & Yoon-Koo Kang

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Contributions

Study concepts: YKK; data acquisition: H-DK, CY, M-HR and Y-KK; quality control of data and algorithms: H-DK, CY, M-HR and Y-KK; data analysis and interpretation: H-DK, CY, M-HR and Y-KK; statistical analysis: H-DK, CY, M-HR and YKK; manuscript preparation: H-DK and Y-KK; manuscript editing: H-DK, CY, M-HR and Y-KK; manuscript review: H-DK, CY, M-HR and Y-KK.

Corresponding author

Correspondence to Yoon-Koo Kang.

Ethics declarations

Competing interests

There are no competing interests directly related to this work. Out of this work, Y-KK has served as a consultant for ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncolgy, BMS, Merck (MSD). M-HR received honoraria from DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Novartis, Daiichi Sankyo and AstraZeneca, and served as a consultant for DAEHWA Pharmaceutical, Bristol Myers Squibb, Lilly and Ono Pharmaceutical. CY received honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen, and received research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Celgene, Ipsen, Boryung Pharmaceuticals, Ildong Pharmaceuticals, CKD Pharmaceuticals, and HK inno.N.

Ethics approval and consent to participate

The protocol of this study was approved by the Institutional Review Board of Asan Medical Center and it was conducted in accordance with the ethical principles of the Declaration of Helsinki and within the Good Clinical Practice Guidelines, as defined by the International Conference on Harmonization. All patients provided written informed consent before enrolment. This study was registered with clinicaltrial.gov (NCT 02712112).

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Kim, HD., Yoo, C., Ryu, MH. et al. A randomised phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumours. Br J Cancer 129, 275–282 (2023). https://doi.org/10.1038/s41416-023-02269-z

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