Effects of capmatinib: A Synthesis of Findings from 20 Studies

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Original Abstract of the Article

Major Research Findings

Capmatinib is a potent and clinically relevant MET inhibitor that has shown efficacy in treating non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations. 1 Capmatinib has been approved by the Food and Drug Administration (FDA) for the treatment of metastatic NSCLC in adults whose tumors have a mutation leading to mesenchymal-epithelial transition exon 14 skipping. 9 Researchers have explored the use of capmatinib as a potential treatment for patients who have developed resistance to other MET inhibitors such as capmatinib and tepotinib. 12 Capmatinib is also being investigated for its potential to enhance the effectiveness of radiation therapy in NSCLC patients with MET exon 14 mutations or MET amplification. 1 Studies have shown that capmatinib can remain in the body for a longer period of time, resulting in prolonged binding to its target protein. 7

Benefits and Risks

Benefit Summary

Capmatinib is a promising treatment option for NSCLC patients with MET exon 14 skipping mutations, as it has demonstrated efficacy in clinical trials. 12 It may also offer a solution for patients who have developed resistance to other MET inhibitors. 12 Capmatinib may enhance the effectiveness of radiation therapy in certain NSCLC patients. 1

Risk Summary

Capmatinib has been linked to liver toxicity, a serious side effect that requires close monitoring. 3 Capmatinib can interact with other medications, potentially leading to adverse effects. 4 , 10 Capmatinib may also impact kidney function, requiring careful evaluation. 10

Comparison Between Studies

Commonalities

Multiple studies have consistently shown that capmatinib is a viable treatment option for NSCLC patients with MET exon 14 skipping mutations. 12 , 1 , 20 , 9 Research also suggests that capmatinib may overcome resistance to other MET inhibitors. 12

Differences

The research findings on capmatinib's liver effects and drug interactions are somewhat inconsistent across studies, highlighting the need for further investigation. 3 , 4 , 10

Consistency and Contradictions of Results

While multiple studies agree on the potential of capmatinib to treat NSCLC patients with MET exon 14 skipping mutations, 12 , 1 , 20 , 9 there is a lack of consensus regarding its side effects and drug interactions. 3 , 4 , 10 Further research is crucial to clarify these discrepancies.

Real-World Application and Considerations

Capmatinib holds promise as a treatment option for NSCLC patients with MET exon 14 skipping mutations, but it's essential to be aware of its potential side effects and drug interactions. 3 , 4 , 10 Open communication with your doctor is vital to discuss any concerns and ensure you understand the risks and benefits of capmatinib treatment.

Current Research Limitations

More research is needed to fully understand the side effects and drug interactions of capmatinib. 3 , 4 , 10 Further investigation is also necessary to determine the effectiveness of capmatinib in treating other types of cancer.

Future Research Directions

Future research should focus on clarifying the side effects and drug interactions of capmatinib. 3 , 4 , 10 Additional research is also needed to determine the efficacy of capmatinib in treating other cancer types.

Conclusion

Capmatinib is a promising treatment option for NSCLC patients with MET exon 14 skipping mutations. 12 , 1 , 20 , 9 However, more research is needed to fully understand its potential side effects and drug interactions. 3 , 4 , 10 It's crucial to consult with your doctor to discuss the risks and benefits of capmatinib treatment before making a decision.

Literature analysis of 20 papers
Positive Content
17
Neutral Content
1
Negative Content
2
Article Type
0
0
0
2
17
1.

MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer.

Author: RameshShrey, CifciAhmet, JaveriSaahil, MinneRachel, LonghurstColin A, NickelKwangok P, KimpleRandall J, BaschnagelAndrew M

Tumor growth inhibition

This study investigated the effects of inhibiting the MET receptor with capmatinib in combination with radiation in NSCLC models. The study found that capmatinib enhances the effect of radiation in both MET exon 14-mutated and MET-amplified NSCLC models.

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

Language : English

2.

Real-World Treatment Outcomes of MET Exon14 Skipping in Non-small Cell Lung Cancer: GFPC 03-18 Study.

Author: BabeyHélène, JammePhilippe, CurcioHubert, AssiéJean Baptiste, VeillonRemi, DoubreHélène, PérolMaurice, GuisierFlorian, HuchotEric, DecroisetteChantal, FalcheroLionel, CorreRomain, CortotAlexis, ChouaïdChristos, DescourtRenaud

No benefit with anti-MET TKIs

A retrospective study of 118 patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping mutations (METexon14) found no evidence of a benefit in overall survival (mOS) with anti-MET tyrosine kinase inhibitors (TKIs). The mOS was 27.1 months (95% CI 18-31.4) with a median follow-up of 16 months (95% CI 13.6-29.7).

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

Language : English

3.

Severe hepatotoxicity during treatment with capmatinib.

Author: Valencia SotoCarmen María, Martínez CallejoVirginia, García-Avello Fernández-CuetoAdela, Villacañas PalomaresMaría Victoria, Barbadillo VillanuevaSara, Ochagavía SufrateguiMaría, López-Brea PiquerasMarta Francisca, Valero DomínguezMarta

Fatal outcome
Severe hepatotoxicity

Capmatinib, a MET inhibitor, can lead to severe hepatotoxicity, a rare but serious adverse drug reaction. Close monitoring of liver function is crucial before and during treatment with capmatinib.

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

Language : English

4.

Cardiac toxicity associated with pharmacokinetic drug-drug interaction between crizotinib and sofosbuvir/velpatasvir: A case report.

Author: MonribotAnthia, HuillardOlivier, KhoudourNihel, PrétaLaure-Hélène, BlanchetBenoit, CabanesLaure, BatistaRui, PalletNicolas, ChouchanaLaurent, GoldwasserFrançois, SogniPhilippe, Thomas-SchoemannAudrey

Hepatitis C treatment
Lung cancer treatment
Cardiac toxicity

This case report describes a drug-drug interaction between crizotinib and sofosbuvir/velpatasvir leading to cardiac toxicity. Crizotinib was well tolerated, but 1 week after sofosbuvir/velpatasvir initiation, the patient experienced bilateral lower-limb edema and dyspnoea. This suggests a reciprocal interaction between crizotinib and velpatasvir, mediated by CYP3A4 and P-glycoprotein.

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

5.

Non-small cell lung cancer with MET exon 14 skip mutation: case report.

Author: CloughWolfgang, Al JaberiMira, DaliaSamir

NSCLC treatment

This abstract provides an overview of non-small cell lung cancer (NSCLC), the most common type of lung cancer. It discusses the different subtypes of NSCLC and traditional treatment approaches, along with the advent of genotype subtype analysis and targeted therapy for personalized treatment options.

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

6.

Single low-dose INC280-loaded theranostic nanoparticles achieve multirooted delivery for MET-targeted primary and liver metastatic NSCLC.

Author: SunYige, YangJie, LiYingbo, LuoJing, SunJiemei, LiDaoshuang, WangYuchen, WangKai, YangLili, WuLina, SunXilin

NSCLC treatment
Off-tumor effects

Capmatinib, a MET inhibitor, shows promise for treating non-small cell lung cancer (NSCLC). However, its poor solubility and off-tumor effects limit its effectiveness.

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

8.

MET-targeted therapies for the treatment of non-small-cell lung cancer: A systematic review and meta-analysis.

Author: XuLinrui, WangFaping, LuoFengming

Improved outcomes
Adverse events

MET inhibitors showed a satisfactory safety profile with a pooled objective response rate (ORR) of 28.1% and disease control rate (DCR) of 69.1% in patients with non-small cell lung cancer (NSCLC). Tepotinib and savolitinib exhibited higher ORRs (44.7% and 42.9%) compared to other MET 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.

Language : English

12.

Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation.

Author: FujinoToshio, SudaKenichi, KogaTakamasa, HamadaAkira, OharaShuta, ChibaMasato, ShimojiMasaki, TakemotoToshiki, SohJunichi, MitsudomiTetsuya

NSCLC treatment

This study explored agents that are active against D1228X and Y1230X MET mutations, which are common mechanisms of resistance to capmatinib and tepotinib, the guideline-recommended treatments for non-small-cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations (METex14).

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

14.

Loss of Tpl2 activates compensatory signaling and resistance to EGFR/MET dual inhibition in v-RAS transduced keratinocytes.

Author: KelleyMary B, GeddesTaylor J, OchiaiMaria, LamplNoah M, KothmannW Wade, FiersteinSara R, KentVictoria, DeCicco-SkinnerKathleen

cSCC treatment

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Tpl2, a tumor suppressor gene, interacts with EGFR and MET signaling pathways, which are involved in cSCC development. Blocking these pathways can lead to resistance, suggesting the need for combination therapy involving both EGFR and MET inhibitors.

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.

Language : English

15.

Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET.

Author: HuangWei-Chieh, YenJia-Hau, SungYu-Wen, TungShiao-Lin, ChenPo-Ming, ChuPei-Yi, ShihYa-Chi, ChiHsiang-Cheng, HuangYi-Ching, HuangShih-Jei, WangLu-Hai

MET targeted therapy
TNBC treatment

Triple negative breast cancer (TNBC) is a type of breast cancer with a poor prognosis. This study identified THEMIS2, a gene that plays a role in promoting cancer stemness in TNBC. The study also found that cryptotanshinone (CPT) can inhibit cancer stemness by suppressing THEMIS2 expression, suggesting a potential new therapeutic approach for TNBC.

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

16.

Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease.

Author: SugiyamaMichael G, CuiHaotian, RedkaDar'ya S, KarimzadehMehran, RujasEdurne, MaanHassaan, HayatSikander, CheungKyle, MisraRahul, McPheeJoseph B, ViirreRussell D, HallerAndrew, BotelhoRoberto J, KarshafianRaffi, SabatinosSarah A, FairnGregory D, Madani TonekaboniSeyed Ali, WindemuthAndreas, JulienJean-Philippe, ShahaniVijay, MacKinnonStephen S, WangBo, AntonescuCostin N

Antiviral activity

This study presents a computational approach to identify new antiviral drug targets and repurpose existing drugs for the treatment of human coronavirus diseases. The approach uses graph convolutional networks and multiscale interactome analysis to predict drug targets and identify potential off-target effects. Experimental validation confirmed the antiviral activity of several repurposed drugs, including the MET inhibitor capmatinib, which exhibited broad antiviral activity against various coronaviruses.

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

18.

Combination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance.

Author: BahcallMagda, PaweletzCloud P, KuangYanan, TausLuke J, SimTaebo, KimNam Doo, DholakiaKshiti H, LauChristie J, GokhalePrafulla C, ChopadePratik R, HongFangxin, WeiZihan, KöhlerJens, KirschmeierPaul T, GuoJiannan, GuoSujuan, WangStephen, JännePasi A

Drug resistance reduction

MET-targeted therapies are effective for treating <i>MET</i>-amplified and <i>MET</i> exon 14 deletion mutant lung cancers. However, resistance to these therapies is a major concern. This study found that combining type I and type II MET tyrosine kinase inhibitors (TKIs) effectively prevented the emergence of drug-resistant clones in vitro and in vivo. These findings suggest that combination therapy may be a valuable approach to overcoming drug resistance in MET-driven lung cancers.

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, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Capmatinib successfully overcomes tepotinib-induced intolerable peripheral edema.

Author: KunimasaKei, KawamuraTakahisa, TamiyaMotohiro, InoueTakako, KuharaHanako, NishinoKazumi, KumagaiToru

Lung cancer treatment
MET inhibition
Peripheral edema

Capmatinib and tepotinib are MET inhibitors approved for metastatic non-small cell lung carcinoma with MET exon 14 skipping alterations. This case report describes a patient who experienced intolerable peripheral edema with tepotinib but tolerated capmatinib after switching. This suggests that MET inhibitors may have different effects on peripheral edema, highlighting the need for individualized management strategies.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer.

Author: DrusboskyLeylah M, DawarRicha, RodriguezEstelamari, IkpeazuChukwuemeka V

MET Exon 14 skipping
NSCLC treatment
TKIs
MET Exon 14 skipping resistance

MET Exon 14 skipping mutation inhibitors, such as capmatinib and tepotinib, have shown significant clinical activity in treating lung cancer patients with this mutation. While these inhibitors can cross the blood-brain barrier, acquired resistance remains a challenge.

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

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