Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors
Prapassorn Thirasastr, Neeta Somaiah Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Neeta Somaiah, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0450, Hou...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-02-01
|
| Series: | Clinical and Experimental Gastroenterology |
| Subjects: | |
| Online Access: | https://www.dovepress.com/emerging-data-on-the-safety-and-efficacy-of-ripretinib-for-the-treatme-peer-reviewed-fulltext-article-CEG |
| _version_ | 1811167732382564352 |
|---|---|
| author | Thirasastr P Somaiah N |
| author_facet | Thirasastr P Somaiah N |
| author_sort | Thirasastr P |
| collection | DOAJ |
| description | Prapassorn Thirasastr, Neeta Somaiah Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Neeta Somaiah, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0450, Houston, TX, 77030, USA, Tel +1 713 792-3626, Email nsomaiah@mdanderson.orgAbstract: In patients with gastrointestinal stromal tumors (GIST), systemic treatment after disease progression on imatinib is challenging. Sunitinib and regorafenib are approved in the second- and third-line setting, respectively, with activity against certain secondary mutations with comparatively much lower response rates and survival increment compared to imatinib. All three of these drugs were serendipitously found to have activity in GIST, starting with imatinib, which was formulated for its ability to inhibit BCR-ABL in chronic myelogenous leukemia. Ripretinib is a drug that was specifically developed as a more potent KIT tyrosine kinase inhibitor (TKI), with broad-spectrum activity against the mutations encountered in GIST. Encouraging responses in early and later lines of treatment in the Phase 1 trial of ripretinib in GIST led to the rapid development of this novel drug. In a Phase 3 randomized clinical trial with cross-over, ripretinib demonstrated superior PFS and overall survival (OS) in 4th-line treatment and beyond compared to placebo. This established 150 mg once daily ripretinib as the standard of care in this setting. Ripretinib is generally well tolerated, with common adverse effects of hair loss, diarrhea, cramps, fatigue and nausea. The favorable safety profile and efficacy of ripretinib prompted its evaluation in a randomized phase 3 trial in the 2nd-line treatment setting. However, it did not result in a longer PFS duration than sunitinib. Although the efficacy of ripretinib in this unselected patient population was not significantly different from that of sunitinib, the tolerability profile was better. This review article aims to review the efficacy and tolerability profile of ripretinib, together with its role in the setting of unresectable or metastatic GIST.Keywords: ripretinib, GIST, systemic treatment in GIST, imatinib-resistant mutation |
| first_indexed | 2024-04-10T16:13:53Z |
| format | Article |
| id | doaj.art-89011bbaf36442a5bcfae95d0793b09b |
| institution | Directory Open Access Journal |
| issn | 1178-7023 |
| language | English |
| last_indexed | 2024-04-10T16:13:53Z |
| publishDate | 2023-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical and Experimental Gastroenterology |
| spelling | doaj.art-89011bbaf36442a5bcfae95d0793b09b2023-02-09T18:41:51ZengDove Medical PressClinical and Experimental Gastroenterology1178-70232023-02-01Volume 16111981534Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal TumorsThirasastr PSomaiah NPrapassorn Thirasastr, Neeta Somaiah Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Neeta Somaiah, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0450, Houston, TX, 77030, USA, Tel +1 713 792-3626, Email nsomaiah@mdanderson.orgAbstract: In patients with gastrointestinal stromal tumors (GIST), systemic treatment after disease progression on imatinib is challenging. Sunitinib and regorafenib are approved in the second- and third-line setting, respectively, with activity against certain secondary mutations with comparatively much lower response rates and survival increment compared to imatinib. All three of these drugs were serendipitously found to have activity in GIST, starting with imatinib, which was formulated for its ability to inhibit BCR-ABL in chronic myelogenous leukemia. Ripretinib is a drug that was specifically developed as a more potent KIT tyrosine kinase inhibitor (TKI), with broad-spectrum activity against the mutations encountered in GIST. Encouraging responses in early and later lines of treatment in the Phase 1 trial of ripretinib in GIST led to the rapid development of this novel drug. In a Phase 3 randomized clinical trial with cross-over, ripretinib demonstrated superior PFS and overall survival (OS) in 4th-line treatment and beyond compared to placebo. This established 150 mg once daily ripretinib as the standard of care in this setting. Ripretinib is generally well tolerated, with common adverse effects of hair loss, diarrhea, cramps, fatigue and nausea. The favorable safety profile and efficacy of ripretinib prompted its evaluation in a randomized phase 3 trial in the 2nd-line treatment setting. However, it did not result in a longer PFS duration than sunitinib. Although the efficacy of ripretinib in this unselected patient population was not significantly different from that of sunitinib, the tolerability profile was better. This review article aims to review the efficacy and tolerability profile of ripretinib, together with its role in the setting of unresectable or metastatic GIST.Keywords: ripretinib, GIST, systemic treatment in GIST, imatinib-resistant mutationhttps://www.dovepress.com/emerging-data-on-the-safety-and-efficacy-of-ripretinib-for-the-treatme-peer-reviewed-fulltext-article-CEGripretinibgistsystemic treatment in gistimatinib-resistant mutation |
| spellingShingle | Thirasastr P Somaiah N Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors Clinical and Experimental Gastroenterology ripretinib gist systemic treatment in gist imatinib-resistant mutation |
| title | Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors |
| title_full | Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors |
| title_fullStr | Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors |
| title_full_unstemmed | Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors |
| title_short | Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors |
| title_sort | emerging data on the safety and efficacy of ripretinib for the treatment of gastrointestinal stromal tumors |
| topic | ripretinib gist systemic treatment in gist imatinib-resistant mutation |
| url | https://www.dovepress.com/emerging-data-on-the-safety-and-efficacy-of-ripretinib-for-the-treatme-peer-reviewed-fulltext-article-CEG |
| work_keys_str_mv | AT thirasastrp emergingdataonthesafetyandefficacyofripretinibforthetreatmentofgastrointestinalstromaltumors AT somaiahn emergingdataonthesafetyandefficacyofripretinibforthetreatmentofgastrointestinalstromaltumors |