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Pimitespib for the treatment of advanced gastrointestinal stromal tumors and other tumors

Toshihiko Doi

Noboru Yamamoto

Shuichi Ohkubo

Toshihiko Doi

*Author for correspondence: Tel.: +81 471 331 111;

E-mail Address: tdoi@east.ncc.go.jp

https://orcid.org/0000-0003-2042-6829

Department of Experimental Therapeutics, National Cancer Centre Hospital East, Kashiwa, Japan

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Noboru Yamamoto

Department of Experimental Therapeutics, National Cancer Centre Hospital, Tokyo, Japan

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Shuichi Ohkubo

https://orcid.org/0000-0001-9554-4534

Discovery and Preclinical Research Division, Taiho Pharmaceutical Co., Ltd, Tsukuba, Ibaraki, Japan

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Published Online:5 Dec 2023https://doi.org/10.2217/fon-2022-1172

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Abstract

Pimitespib (TAS-116) is the first heat shock protein 90 (HSP90) inhibitor approved in Japan, and it is indicated for the treatment of gastrointestinal stromal tumors (GIST) that have progressed after treatment with imatinib, sunitinib and regorafenib. This review describes the preclinical and clinical research with pimitespib, including its mechanism of action, pharmacokinetics, clinical antitumour activity and safety. In a phase III study, pimitespib significantly prolonged progression-free survival compared with placebo (median 2.8 vs 1.4 months; hazard ratio 0.51; 95% CI 0.30–0.87; p = 0.006). Common treatment-related adverse events were diarrhoea, decreased appetite, increase in serum creatinine, malaise, nausea and eye disorders. The efficacy and safety of pimitespib are being investigated in other tumour types and in combination with other anticancer therapies.

Plain language summary – A summary of the new anticancer drug, pimitespib, for treating gastrointestinal stromal tumors that are unresponsive to initial treatments & have spread to other parts of the body

What is this article about?

This article provides information about pimitespib, a drug that recently became available in Japan for the treatment of advanced gastrointestinal stromal tumors, or ‘GISTs’. GISTs are a type of cancer found in the gastrointestinal tract, and those that are considered ‘advanced’ have stopped responding to other treatments and have spread to other parts of the body.

What have studies shown?

Pimitespib works in a way unlike other drug treatments for cancer – it inhibits a protein called heat shock protein 90, and this stops cancer cells from developing and growing. Pimitespib is taken by mouth. Studies in Japanese patients with advanced GISTs showed an increase in the time taken for the cancer to progress further and in the length of time that patients survived among those treated with pimitespib, compared with patients who did not receive the drug. These studies also found that pimitespib was not associated with serious side effects, although diarrhoea occurred frequently. Eye disorders developed in some patients, but they could be managed by interrupting or stopping treatment with pimitespib. Pimitespib is also being studied for the treatment of other cancers, alone and in combination with other anticancer drugs.

What conclusions can be made from these studies?

There are very few treatments available for patients with advanced GISTs and, therefore, pimitespib is an important new option for such patients in Japan. If the results of ongoing studies are positive, pimitespib may become a treatment option for a wider range of cancer patients in the future.

Tweetable abstract

Check out our latest review examining the therapeutic potential and safety of the HSP90 inhibitor #pimitespib for advanced #gastrointestinalstromaltumors and other forms of cancer.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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History

Received 24 November 2022

Accepted 7 September 2023

Published online 5 December 2023

Published in print March 2024

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Keywords

Author contributions

All authors developed the concept for the review, S Ohkubo searched and analysed the literature, and T Doi, N Yamamoto and S Ohkubo reviewed and revised the paper. All authors approved the final draft of the manuscript for submission.

Financial disclosure

This article was supported by Taiho. T Doi has received research grants from Abbvie, BMS, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo, Eisai, IQVIA, Janssen Pharma, Lilly, Merck Biopharma, MSD, Novartis, Pfizer, Sumitomo Dainippon and Taiho; honoraria from AstraZeneca, BMS, Daiichi Sankyo, Rakuten Medical and Ono Pharma; consulting fees from Abbvie, Bayer, Chugai Pharma, Kaken Pharma, Kyowa Kirin, Otsuka Pharma, PRA Health Science, Rakuten Medical, Shionogi, Sumitomo Dainippon, Takeda and Taiho; and has served on advisory boards for Abbvie, Amgen, Astellas Pharma, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Janssen Pharma, MSD and Novartis. N Yamamoto has received research grants from Astellas, Bayer, BMS, Boehringer Ingelheim, Carna Biosciences, Chiome Bioscience Inc., Chugai, Daiichi-Sankyo, Eisai, Genmab, GSK, Janssen Pharma, Kyowa-Hakko Kirin, Lilly, Merck, MSD, Novartis, Ono Pharmaceutical Co., Ltd, Otsuka, Pfizer, Quintiles, Shionogi, Sumitomo Dainippon, Taiho, Takeda and Toray; honoraria from AstraZeneca, BMS, Chugai, Eisai, Ono Pharmaceutical Co., Ltd, Pfizer and Sysmex; and consulting fees from Boehringer Ingelheim, Cimic, Eisai, Otsuka and Takeda. S Ohkubo is a full-time employee of Taiho Pharmaceutical Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

Medical writing support was provided by Catherine Rees on behalf of inScience Communications, Springer Healthcare, and was funded by Taiho Pharmaceuticals.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

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