Effects of repotrectinib: A Synthesis of Findings from 10 Studies

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Original Abstract of the Article

Major Research Findings

Repotrectinib is a promising drug for the treatment of TRK fusion-positive cancers. 9 Repotrectinib is a next-generation TRK kinase inhibitor and shows potential to overcome resistance to conventional drugs such as larotrectinib and entrectinib. 9 Repotrectinib exhibits potent inhibitory effects against both wild-type and mutant TRK and possesses excellent pharmacokinetic properties. 9 Repotrectinib has been shown to induce remission in patients who failed larotrectinib treatment. 9 Repotrectinib has also been found to be effective in treating ROS1 fusion-positive non-small cell lung cancer. 4 It demonstrates anti-tumor effects even in patients with the crizotinib-resistant ROS1-G2032R mutation. 4 Repotrectinib shows promise for treating neuroblastoma as well. 5 It effectively inhibits signaling activity of a range of ALK mutant variants found in neuroblastoma patients and exhibits strong anti-tumor effects in a xenograft model of neuroblastoma. 5

Benefits and Risks

Benefits Summary

Repotrectinib holds great potential as a new treatment for various cancers, including TRK fusion-positive cancers, ROS1 fusion-positive non-small cell lung cancer, and neuroblastoma. 9 4 5 It could overcome resistance to conventional medications and offer new therapeutic opportunities for patients.

Risks Summary

Repotrectinib, being a TRK pathway inhibitor, may cause side effects such as weight gain, dizziness/ataxia, and paresthesias. 6 However, repotrectinib is generally considered a safe drug, and these side effects are usually mild to moderate. 6 Careful monitoring for these side effects is necessary while using repotrectinib.

Study Comparisons

Study Similarities

Multiple studies have demonstrated repotrectinib's efficacy against a variety of cancers, including TRK fusion-positive cancers, ROS1 fusion-positive non-small cell lung cancer, and neuroblastoma. 9 4 5 These studies suggest that repotrectinib could provide a new treatment option for these cancers.

Study Differences

Each study focused on different cancer types and administered repotrectinib using various methods. 9 4 5 Therefore, direct comparison of the results from these studies is difficult.

Consistency and Contradictions in the Results

Multiple studies have consistently shown that repotrectinib is effective in treating TRK fusion-positive cancers, ROS1 fusion-positive non-small cell lung cancer, and neuroblastoma. 9 4 5 However, since the studies focused on different cancer types and administered repotrectinib using various methods, direct comparison of the results is challenging. 9 4 5 Further research is needed.

Application to Daily Life and Precautions

Repotrectinib is a promising drug for the treatment of TRK fusion-positive cancers, ROS1 fusion-positive non-small cell lung cancer, and neuroblastoma. 9 4 5 However, repotrectinib can cause side effects such as weight gain, dizziness/ataxia, and paresthesias. 6 It's crucial to monitor these side effects closely when using repotrectinib.

Limitations of the Current Research

Research on repotrectinib is still in its early stages, and further investigation is needed to assess its long-term effects and safety. 9 4 5 More detailed information regarding resistance to repotrectinib and the incidence of side effects is also required.

Future Research Directions

Further research is necessary, including studies on the long-term effects and safety of repotrectinib, resistance to repotrectinib, and the incidence of side effects. 9 4 5 These studies will contribute to a deeper understanding of the clinical utility of repotrectinib.

Conclusion

Repotrectinib holds promise as a treatment option for a variety of cancers, including TRK fusion-positive cancers, ROS1 fusion-positive non-small cell lung cancer, and neuroblastoma. 9 4 5 However, research on repotrectinib is still in its early stages, and further investigation is needed to fully assess its long-term effects and safety. 9 4 5 Additional research is necessary to gain a more comprehensive understanding of the clinical utility of repotrectinib.

Literature analysis of 10 papers
Positive Content
10
Neutral Content
0
Negative Content
0
Article Type
3
0
0
3
10
1.

Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM.

Author: WolffenbuttelB H, NijstL, SelsJ P, MenheereP P, MüllerP G, KrusemanA C

Diabetes treatment
Repaglinide effective

Repaglinide, a new oral hypoglycaemic agent, effectively lowered postprandial blood glucose levels in patients with NIDDM. In a study of 44 patients, repaglinide was more effective than glibenclamide in reducing postprandial blood glucose. Both drugs reduced total cholesterol levels. Repaglinide was well-tolerated with no significant side effects observed.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide.

Author: NiemiM, NeuvonenP J, KivistöK T

Lower blood glucose
Hypoglycemia

Clarithromycin was found to increase the plasma concentrations and effects of repaglinide. Clarithromycin increased the area under the concentration-time curve of repaglinide by 40% and the peak plasma concentration by 67%. Concomitant use of clarithromycin or other potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.

Author: KajosaariLauri I, BackmanJanne T, NeuvonenMikko, LaitilaJouko, NeuvonenPertti J

Lower blood glucose

Gemfibrozil is a drug that lowers cholesterol and increases the effects of the diabetes drug repaglinide. This study will examine the effects of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naïve and Solvent-Front-Mutant ROS1-Rearranged Non-Small Cell Lung Cancer.

Author: YunMi Ran, KimDong Hwi, KimSeok-Young, JooHyeong-Seok, LeeYou Won, ChoiHun Mi, ParkChae Won, HeoSeong Gu, KangHan Na, LeeSung Sook, SchoenfeldAdam J, DrilonAlexander, KangSeok-Gu, ShimHyo Sup, HongMin Hee, CuiJ Jean, KimHye Ryun, ChoByoung Chul

ROS1+ lung cancer treatment

This study investigated the antitumor activity of repotrectinib, a novel next-generation ROS1/TRK/ALK-tyrosine kinase inhibitor (TKI), in ROS1+ patient-derived preclinical models. Repotrectinib showed promising antitumor activity against crizotinib-resistant ROS1-G2032R (ROS1G2032R) mutation and CNS progression.

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

5.

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.

Author: Cervantes-MadridDiana, SzydzikJoanna, LindDan Emil, BorenäsMarcus, BemarkMats, CuiJean, PalmerRuth Helen, HallbergBengt

Strong antitumor effects

This study investigated the effects of repotrectinib, a third-generation ALK inhibitor, in neuroblastoma. Repotrectinib inhibited ALK signaling in vitro and exhibited strong antitumor effects in a neuroblastoma xenograft model.

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

6.

TRK inhibitors in TRK fusion-positive cancers.

Author: DrilonA

Brain metastasis treatment
TRK fusion-positive cancer
Dizziness
Weight gain

TRK fusions are oncogenic drivers of various cancers. First-generation TRK inhibitors, larotrectinib and entrectinib, have shown efficacy in treating TRK fusion-positive cancers, including those with brain metastases. Next-generation TRK inhibitors, such as selitrectinib and repotrectinib, are being developed to address on-target resistance. TRK inhibitors have a favorable safety profile, but certain on-target adverse events should be monitored in the clinic.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

TRK inhibitors in TRK fusion-positive cancers.

Author: DrilonA

Durable responses
Intracranial activity
Dizziness
Paraesthesias
Weight gain

TRK inhibitors, such as larotrectinib and entrectinib, are effective in treating various cancers with TRK fusions, including those with brain metastases. While resistance can occur, next-generation inhibitors like selitrectinib and repotrectinib are being developed to overcome this. Although TRK inhibitors have a good safety profile, some on-target side effects like weight gain and dizziness can occur.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

TRK inhibitor activity and resistance in TRK fusion-positive cancers in adults.

Author: HaradaGuilherme, DrilonAlexander

TRK fusion cancer treatment
TRK inhibitor side effects

TRK inhibitors, such as larotrectinib and entrectinib, demonstrate high response rates and durable disease control in TRK fusion-positive cancers, including intracranial activity. On-target side effects include dizziness, weight gain, and withdrawal pain. Resistance mechanisms have led to the development of next-generation TRK inhibitors.

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.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

9.

Discovery of the Next-Generation Pan-TRK Kinase Inhibitors for the Treatment of Cancer.

Author: LiuZongliang, YuPengfei, DongLin, WangWenyan, DuanSijin, WangBingsi, GongXiaoyan, YeLiang, WangHongbo, TianJingwei

Cancer treatment

This study reports the identification and optimization of a series of macrocyclic compounds as potent pan-Trk inhibitors. Compound 10 showed good activity against wild and mutant TrkA/TrkC in in vitro and in vivo studies, making it a promising candidate for the treatment of TRK-driven cancers.

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

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