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Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy

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Abstract

Ripretinib (Qinlock®) is a small molecule inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) and is approved for the treatment of gastrointestinal stromal tumours as a fourth-line of therapy. After successive cycles of treatment, gastrointestinal stromal tumours can carry a wide array of mutations, which makes resistance to treatment more likely. Ripretinib has a dual mechanism of action that allows it to target a broad spectrum of mutations in KIT or PDGFRA. The pivotal phase III INVICTUS trial demonstrated an increase of progression-free survival in patients receiving ripretinib compared with placebo, with efficacy being maintained across patients with KIT exon 9, 11, 13 and 17 mutations. Ripretinib has acceptable tolerability, with the most common drug-related grade 3 or 4 adverse events being lipase increases, hypertension, fatigue and hypophosphataemia. Ripretinib is therefore a valuable additional line of therapy available for the management of gastrointestinal stromal tumours.

Plain Language Summary

The receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) regulate cell growth and survival; mutations in the genes of these proteins are the most common causes of gastrointestinal stromal tumours. Drugs that target kinases are a mainstay in the treatment of these cancers; however, new mutations often occur that make tumours resistant to kinase inhibitors. Ripretinib (Qinlock®) is approved for patients with gastrointestinal stromal tumours after the tumour has become resistant to three or more other kinase inhibitors. In a pivotal phase III clinical trial in patients with gastrointestinal stromal tumours and who had failure with three or more prior treatments, ripretinib significantly delayed disease progression compared with placebo. Ripretinib has an acceptable side effect profile, with the most common drug-related side effects being alopecia, muscle pain and nausea. Thus, ripretinib is a valuable treatment option in the management of advanced gastrointestinal stromal tumours.

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Acknowledgments

During the peer review process, the manufacturer of ripretinib was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Simon Fung & Matt Shirley

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  1. Simon Fung
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Correspondence to Simon Fung.

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The preparation of this review was not supported by any external funding.

Authorship and conflict of interest

S. Fung and M. Shirley are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Additional information

The manuscript was reviewed by: Y. Hayashi, Enteric Neuroscience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA; C.-N. Yeh, General Surgery Department and Liver Research Center, Chang Gung Memorial Hospital, Chang Gung University.

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Fung, S., Shirley, M. Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy. Drugs 82, 1541–1548 (2022). https://doi.org/10.1007/s40265-022-01794-0

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