Effects of ripretinib: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Ripretinib is a tyrosine kinase inhibitor that has been investigated as a treatment for advanced gastrointestinal stromal tumors (GIST) after previous treatment with imatinib. 6 found no significant difference in progression-free survival between ripretinib and sunitinib in patients with GIST who had previously been treated with imatinib. However, 18 demonstrated that ripretinib was more effective in slowing down the progression of GIST compared to sunitinib. Additionally, ripretinib has been reported to have a better tolerability profile with fewer side effects compared to sunitinib. 7

Ripretinib has also shown effectiveness in treating patients with KIT-altered metastatic melanoma, as indicated by 20 .

Ripretinib is approved as a fourth-line therapy for adults with advanced GIST after prior treatment with 3 or more kinase inhibitors, including imatinib. 12

Benefits and Risks

Benefit Summary

Ripretinib has the potential to be an effective treatment option for patients who have developed advanced GIST after treatment with imatinib. 6 did not find a significant difference in progression-free survival compared to sunitinib, however, 18 showed that ripretinib was more effective in slowing down the progression of GIST compared to sunitinib. Additionally, ripretinib has been reported to have a better tolerability profile with fewer side effects compared to sunitinib. 7

Risk Summary

Research indicates that ripretinib may cause skeletal muscle toxicity. 10 Additionally, it is crucial to be aware of potential drug-drug interactions with ripretinib. 9 Common side effects of ripretinib can include hair loss, diarrhea, cramps, fatigue, and nausea. 14 Ripretinib is metabolized by CYP3A4/5, so caution is advised when co-administering with drugs that inhibit CYP3A4/5. 1

Comparison of Studies

Similarities

Several studies have investigated the potential effectiveness of ripretinib in treating patients who have developed advanced GIST following treatment with imatinib. These studies assessed the efficacy and safety of ripretinib.

Differences

The studies differ in their selection of comparison treatments, patient demographics, and research designs. 6 and 18 both compared ripretinib to sunitinib; however, the specific study designs and patient characteristics varied, potentially influencing the outcomes. 20 investigated ripretinib in patients with metastatic melanoma, unlike the other studies focusing on GIST.

Consistency and Discrepancies in Findings

Multiple studies suggest that ripretinib holds promise as a potential treatment option for patients with advanced GIST after imatinib therapy. However, some inconsistencies arise in comparisons of ripretinib to sunitinib. These inconsistencies may be attributed to variations in study design, patient characteristics, and other factors.

Considerations for Real-World Application

Ripretinib shows potential as a treatment for advanced GIST following imatinib therapy; however, it is important to be aware of its associated risks. When considering ripretinib treatment, it is crucial to follow the recommendations of your healthcare provider and regularly monitor for any potential side effects. Also, it's essential to discuss with your doctor any other medications you are currently taking, as ripretinib may interact with other drugs.

Limitations of Current Research

Given its relatively recent introduction, ripretinib requires further research to comprehensively evaluate its long-term efficacy and safety. Additionally, further investigation is needed to understand patient characteristics that might predict responsiveness to ripretinib and to evaluate its potential in combination therapies.

Future Research Directions

Future research should focus on evaluating the long-term efficacy and safety of ripretinib. Additional research is needed to determine which patients are most likely to benefit from ripretinib and to evaluate its effectiveness in combination therapies with other treatments.

Conclusion

Ripretinib shows potential as a treatment option for advanced GIST following imatinib therapy, but it is essential to consider its associated risks. It is crucial to consult with your healthcare provider and carefully monitor for any potential side effects. Future research is needed to further evaluate the effectiveness and safety of ripretinib.

Literature analysis of 22 papers
Positive Content
22
Neutral Content
0
Negative Content
0
Article Type
2
1
0
6
18
1.

Effects of CYP3A Inhibition, CYP3A Induction, and Gastric Acid Reduction on the Pharmacokinetics of Ripretinib, a Switch Control KIT Tyrosine Kinase Inhibitor.

Author: LiXiaoyan, SheltonMark J, WangJing, MeadeJulie, Ruiz-SotoRodrigo

Effective for advanced GIST
Drug interactions

This study evaluated the drug-drug interaction potential of ripretinib, a KIT kinase inhibitor, with itraconazole, rifampin, and pantoprazole. Itraconazole increased ripretinib exposure, while rifampin decreased it. Pantoprazole had no effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

Author: LiJian, ZhangJun, ZhangYanqiao, QiuHaibo, ZhouYanbing, ZhouYongjian, ZhangXinhua, ZhouYe, ZhuYuping, LiYong, WangMing, ShenKuntang, TaoKaixiong, WuXin, WangHaijiang, ZhangBo, LingJiayu, YeYingjiang, WuXingye, QuHongyan, MaYue, JiaoXuelong, ZhengHualong, JinJiejie, LiuZhuo, TanMing, FangYong, ZhangPeng, ZhangNan, LeiCheng, CaiZhaolun, LiangBin, PengZhangyan, HuangZhao, DongJuan, ShenLin

GIST treatment

Ripretinib demonstrated similar efficacy and a favorable safety profile compared to sunitinib as second-line treatment for Chinese patients with gastrointestinal stromal tumors. Ripretinib provided greater benefit than sunitinib in patients with KIT exon 11 mutations.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Medication guide for dose adjustment and management of cardiotoxicity and lipid metabolic adverse events of oral antineoplastic therapy.

Author: Ramos-RuperezElena, Escudero-VilaplanaVicente, Ruiz-BrionesPaula, Collado-BorrellRoberto, Villanueva-BuenoCristina, Revuelta-HerreroJosé Luis, González-HabaEva, Garcia-GonzalezXandra, Ibañez-GarciaSara, Perez-RamirezSara, Zatarain-NicolásEduardo, HerranzAna, SanjurjoMaría

Cardiotoxicity management
OAA prescribing

This article provides a medication management guide for healthcare professionals who prescribe oral antineoplastic agents (OAAs) for cancer treatment. The guide focuses on managing cardiotoxicity and lipid metabolic side effects associated with OAAs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours.

Author: GolčićMarin, JonesRobin L, HuangPaul, NapolitanoAndrea

Improved survival
Personalized treatment
Medication side effects

यो लेखले ग्यास्ट्रोइन्टेस्टाइनल स्ट्रोमल ट्युमर (GIST) को उपचार को लागि सामान्य उपचार योजनाहरू को सिंहावलोकन प्रदान गर्छ।

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study.

Author: GelderblomHans, JonesRobin L, BlayJean-Yves, GeorgeSuzanne, von MehrenMargaret, ZalcbergJohn R, KangYoon-Koo, RazakAlbiruni Abdul, TrentJonathan, AttiaSteven, Le CesneAxel, SiontisBrittany L, GoldsteinDavid, BoyeKjetil, SanchezCesar, SteeghsNeeltje, RutkowskiPiotr, DrutaMihaela, SerranoCésar, SomaiahNeeta, ChiPing, HarrowBrooke, BeckerClaus, ReichmannWilliam, ShermanMatthew L, Ruiz-SotoRodrigo, HeinrichMichael C, BauerSebastian,

Improved HRQoL
Reduced toxicity
Constipation

Ripretinib provided better HRQoL compared to sunitinib in patients with advanced GIST previously treated with imatinib. Ripretinib may offer clinically meaningful benefit to these patients.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Efficacy of post-first-line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta-analysis.

Author: HuKehan, ZhangHu, ShuMingrong, WangXingyue

GIST treatment

Imatinib is the standard first-line treatment for advanced gastrointestinal stromal tumors (GISTs). However, many patients develop resistance, requiring alternative therapies. This study highlights the need for further research to compare the clinical efficacy of different post-first-line treatments for imatinib-resistant GIST.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Ripretinib for the treatment of adult patients with advanced gastrointestinal stromal tumors.

Author: SargsyanAmalya, KucharczykMonika A, JonesRobin L, ConstantinidouAnastasia

GIST treatment

Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor of the gastrointestinal tract. Imatinib mesylate is the standard first-line therapy for advanced/metastatic GIST, but resistance often develops. This study explores the potential of ripretinib, a type II kinase inhibitor targeting KIT and PDGFRA mutations, as a treatment option for GIST patients who have developed resistance to imatinib.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Progression of the tumor in a patient with a gastrointestinal stromal tumor with the <i>PDGFRA</i> exon 12 mutation who received multiple surgeries and multiple lines of tyrosine kinase inhibitor therapies: a case report.

Author: AnZhaojie, TanMing, XiaYuxiang, LiYong, FanLiqiao, ZhaoQun, ZhangZhidong, TanBibo, LiuYu, MaZhixue, WangDong, ZhaoXuefeng

GIST treatment

This case report describes the treatment of a rare gastrointestinal stromal tumor (GIST) with <i>PDGFRA</i> exon 12 mutations using multiline tyrosine kinase inhibitors (TKIs), including ripretinib. It provides insight into the management of this specific GIST subtype.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

17.

Metastatic SDH-Deficient GIST Diagnosed during Pregnancy: Approach to a Complex Case.

Author: ChennoufAnas, ZeidanElie, BorduasMartin, Noël-LamyMaxime, KremastiotisJohn, BeaudoinAnnie

This is the first case report of a metastatic SDH-deficient GIST in a 23-year-old pregnant patient. The case highlights the complexities of managing GI malignancy during pregnancy, particularly in the context of metastatic WT-GISTs. It emphasizes the need for multidisciplinary care and better clinical guidelines.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

18.

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial.

Author: BauerSebastian, JonesRobin L, BlayJean-Yves, GelderblomHans, GeorgeSuzanne, SchöffskiPatrick, von MehrenMargaret, ZalcbergJohn R, KangYoon-Koo, RazakAlbiruni Abdul, TrentJonathan, AttiaSteven, Le CesneAxel, SuYing, MeadeJulie, WangTao, ShermanMatthew L, Ruiz-SotoRodrigo, HeinrichMichael C

GIST efficacy

Ripretinib is a new tyrosine kinase inhibitor (TKI) that shows comparable effectiveness and safety to sunitinib in patients with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Efficacy and safety of ripretinib in patients with KIT-altered metastatic melanoma.

Author: JankuF, BauerS, ShoumariyehK, JonesR L, SpreaficoA, JenningsJ, PsoinosC, MeadeJ, Ruiz-SotoR, ChiP

KIT-altered melanoma

This study investigates the efficacy and safety of ripretinib, a broad-spectrum KIT and platelet-derived growth factor receptor A inhibitor, in patients with KIT-altered metastatic melanoma enrolled in the expansion phase of a phase I trial.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature.

Author: van de WalDeborah, ElieMai, Le CesneAxel, FumagalliElena, den HollanderDide, JonesRobin L, MarquinaGloria, SteeghsNeeltje, van der GraafWinette T A, HussonOlga

Improved HRQoL
Increased survival
TKI side effects

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of gastrointestinal stromal tumors (GISTs) and have significantly improved overall survival. However, TKIs can also have side effects. This review summarizes the available literature on health-related quality of life (HRQoL) issues and side effects of different TKIs used to treat GIST.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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