Effects of dacomitinib: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Dacomitinib, an EGFR inhibitor, has shown promise in treating various cancers. 17 showed that dacomitinib reduced cell necrosis and increased cell apoptosis in a C6 glioma rat model. It has also been found to inhibit the growth and invasiveness of chemoresistant ovarian carcinoma cells 15 , suppress the proliferation and invasion of pancreatic ductal adenocarcinoma cells 20 , and may be effective in attenuating pulmonary vascular remodeling and pulmonary hypertension 27 . Furthermore, combining dacomitinib with other drugs can enhance its anti-cancer effects, as shown by the study combining dacomitinib with cepharanthine for non-small cell lung cancer 4 . Dacomitinib may also have potential in overcoming resistance to other EGFR inhibitors like osimertinib 23 and is approved for first-line treatment of patients with EGFR-mutated metastatic non-small cell lung cancer 2 .

Despite its promising benefits, dacomitinib also has potential risks. 7 revealed that dacomitinib, like other EGFR tyrosine kinase inhibitors, can lead to hepatotoxicity. Moreover, 10 found that dacomitinib might affect the pharmacokinetics of poziotinib.

Benefits and Risks

Benefit Summary

Dacomitinib has shown potential in treating various cancers, including lung cancer, ovarian cancer, and pancreatic cancer. It may be particularly effective in targeting EGFR-mutated cancers. Dacomitinib can be used in combination with other therapies to enhance its anti-cancer effects. It also has shown promise in overcoming resistance to other EGFR inhibitors.

Risk Summary

Dacomitinib can cause side effects such as hepatotoxicity. It may also interact with other medications. Further research is necessary to fully understand its risks and benefits.

Comparison Between Studies

Commonalities Between Studies

The majority of research on dacomitinib focuses on its ability to target EGFR and inhibit cancer cell growth. Additionally, many studies have highlighted the potential benefits of combining dacomitinib with other therapies to improve treatment outcomes.

Differences Between Studies

While the studies generally agree on the potential of dacomitinib, they differ in terms of the specific cancers studied, the effectiveness of the drug, the identified side effects, and the effectiveness of different combination therapies. Therefore, individualized assessment and careful consideration are necessary when using dacomitinib in clinical settings.

Consistency and Contradictions in Results

Although dacomitinib holds promise for treating specific cancers, inconsistencies exist among the results of various studies. Further research is required to fully understand the drug's effectiveness, safety, and optimal application for various cancer types.

Cautions for Real-Life Application

Dacomitinib should only be used under the guidance of a physician. Individuals should be aware of potential side effects like liver damage. Also, potential drug interactions must be carefully considered.

Current Research Limitations

The research on dacomitinib remains limited. More studies are needed to comprehensively understand its effectiveness, safety, and optimal application in treating various cancers. Further research is also needed on combination therapies, optimal dosing, and the mechanisms of resistance.

Future Research Directions

Further research is necessary to delve deeper into the effectiveness and safety of dacomitinib, including its efficacy in various cancer types, optimal combination therapies, and dosing schedules. Investigating resistance mechanisms to dacomitinib is also crucial for maximizing its therapeutic potential.

Conclusion

Dacomitinib has shown potential for treating different types of cancers, especially those with EGFR mutations. However, research on dacomitinib is ongoing and more studies are needed to confirm its effectiveness and safety for various cancers and to explore potential combinations and dosing strategies. If considering dacomitinib treatment, it is essential to consult with a qualified healthcare professional to discuss the potential benefits and risks.

Literature analysis of 27 papers
Positive Content
26
Neutral Content
0
Negative Content
1
Article Type
1
2
1
6
27
1.

Dacomitinib: First Global Approval.

Author: ShirleyMatt

EGFR-mutated NSCLC treatment

Dacomitinib, a small-molecule inhibitor of HER1 (EGFR), HER2, and HER4, received its first global approval for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutations.

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

2.

Dacomitinib for the first-line treatment of patients with EGFR-mutated metastatic non-small cell lung cancer.

Author: SantarpiaMariacarmela, MenisJessica, ChaibImane, Gonzalez CaoMaria, RosellRafael

Treat NSCLC
Toxicity

Dacomitinib is a second-generation pan-HER inhibitor that has been shown to improve progression-free survival and overall survival compared to gefitinib, a first-generation EGFR TKI, in patients with EGFR-mutated non-small cell lung cancer.

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

3.

Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer.

Author: TanWeiwei, GiriNagdeep, QuinnSusan, WilnerKeith, ParivarKourosh

No clinically relevant effect on ECG parameters

This study investigated the effect of dacomitinib, an EGFR inhibitor, on ECG parameters in patients with non-small cell lung cancer. The study found no clinically relevant effect of dacomitinib on ECG parameters at therapeutic doses.

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

Language : English

6.

Targeting the EGFR signaling pathway in cancer therapy: What's new in 2023?

Author: HalderSushanta, BasuSoumi, LallShobhit P, GantiApar K, BatraSurinder K, SeshacharyuluParthasarathy

Cancer treatment

This article provides an overview of epidermal growth factor receptor (EGFR) and its role in cancer development. EGFR is frequently amplified, overexpressed, and mutated in various cancers, leading to increased kinase activity that promotes uncontrolled proliferation and survival. The article describes the discovery and clinical efficacy of molecular agents targeting the EGFR pathway, highlighting the 14 currently approved EGFR-targeted agents for cancer treatment.

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, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

7.

Hepatotoxicity with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients: A network meta-analysis.

Author: WuZiyang, ChenSuhua, DuXin, WuYibo, XieXiaohui

NSCLC treatment
Hepatotoxicity

A network meta-analysis compared the hepatotoxicity of different EGFR-TKIs used for non-small-cell lung cancer (NSCLC). The analysis found that erlotinib was associated with lower hepatotoxicity compared to other EGFR-TKIs, including gefitinib, afatinib, and osimertinib.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050).

Author: ChengYing, MokTony S, ZhouXiangdong, LuShun, ZhouQing, ZhouJianying, DuYingying, YuPing, LiuXiaoqing, HuChengping, LuYou, ZhangYiping, LeeKi Hyeong, NakagawaKazuhiko, LinkeRolf, WongChew Hooi, TangYiyun, ZhuFanfan, WilnerKeith D, WuYi-Long

Dacomitinib efficacy
OS improvement
PFS prolongation
Adverse events

Dacomitinib is associated with a significant prolongation of progression-free survival (PFS) and improved overall survival (OS) compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC.

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.
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

10.

Effects of dacomitinib on the pharmacokinetics of poziotinib <i>in&#160;vivo</i> and <i>in&#160;vitro</i>.

Author: JiWeiping, ShenJiquan, WangBo, ChenFeifei, MengDeru, WangShuanghu, DaiDapeng, ZhouYunfang, WangChangxiong, ZhouQuan

Drug interaction

Dacomitinib increased the AUC, Cmax, and Tmax of poziotinib in rats, suggesting a potential drug-drug interaction.

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

Language : English

11.

Discovery of novel potent covalent inhibitor-based EGFR degrader with excellent in vivo efficacy.

Author: ShiShi, DuYu, HuangLei, CuiJiaqi, NiuJing, XuYungen, ZhuQihua

Antitumor efficacy
EGFR degradation

This study reports the discovery of Dacomitinib-based EGFR degraders, specifically compound 13, which effectively induces degradation of EGFRdel19 in HCC-827 cells.

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.

Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo.

Author: GuoXiaoran, ToKenneth K W, ChenZhen, WangXiaokun, ZhangJianye, LuoMin, WangFang, YanShirong, FuLiwu

Overcome MDR

This article discusses the role of ABCG2 in multidrug resistance (MDR) in cancer cells. Inhibiting ABCG2 is a promising approach to overcome MDR, but finding a safe and effective inhibitor remains a challenge.

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

Language : English

13.

Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer.

Author: PoelsKamrine E, SchoenfeldAdam J, MakhninAlex, TobiYosef, WangYuli, Frisco-CabanosHeidie, ChakrabartiShaon, ShiManli, NapoliChelsi, McDonaldThomas O, TanWeiwei, HataAaron, WeinrichScott L, YuHelena A, MichorFranziska

Dacomitinib
Lung Cancer Treatment
Osimertinib

This study used computational modeling and experimental data to identify an optimal dosing schedule for the combination therapy of osimertinib and dacomitinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC). The proposed schedule was subsequently validated in a clinical trial.

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 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.
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

15.

Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells.

Author: MomenyMajid, ZarrinradGhazaleh, MoghaddaskhoFarima, PoursheikhaniArash, SankanianGhazaleh, ZaghalAzam, MirshahvaladiShahab, EsmaeiliFatemeh, EyvaniHaniyeh, BarghiFarinaz, SabourinejadZahra, AlishahiZivar, YousefiHassan, GhasemiReza, DardaeiLeila, BashashDavood, ChahardouliBahram, DehpourAhmad R, Tavakkoly-BazzazJavad, AlimoghaddamKamran, GhavamzadehArdeshir, GhaffariSeyed H

EOC treatment

This study investigates the anti-tumor effects of dacomitinib, a pan-ErbB receptor inhibitor, in chemoresistant epithelial ovarian cancer (EOC) cells. Dacomitinib significantly inhibited growth, clonogenic potential, anoikis resistance, and induced apoptosis in these cells. It also attenuated migration and invasion by inhibiting the PLK1-FOXM1 signaling pathway and reducing EMT markers. This suggests that dacomitinib could be a promising therapeutic agent for chemoresistant EOC.

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.

Brain Distribution of a Panel of Epidermal Growth Factor Receptor Inhibitors Using Cassette Dosing in Wild-Type and <i>Abcb1/Abcg2</i>-Deficient Mice.

Author: KimMinjee, LaramyJanice K, MohammadAfroz S, TaleleSurabhi, FisherJames, SarkariaJann N, ElmquistWilliam F

Brain delivery

This study evaluated the brain penetrability of eight epidermal growth factor receptor (EGFR) inhibitors using cassette dosing to identify optimal compounds for treating brain tumors. The study found that two efflux transporters at the blood-brain barrier significantly influence the brain distribution of these inhibitors, informing the choice of EGFR inhibitors that may be effective in future clinical trials for brain tumors.

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

17.

Investigation of dacomitinib on reducing cell necrosis and enhancing cell apoptosis in C6 glioma rat model by MRI.

Author: ChenWang-Sheng, HongLan, WangFei, LiJian-Jun

Glioma tumor necrosis

Dacomitinib, a drug that inhibits the epidermal growth factor receptor (EGFR), has shown promise in treating glioma, a type of brain cancer. This study investigates the regional effects of Dacomitinib on tumor necrosis.

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.

A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors.

Author: EndersbyRaelene, WhitehouseJacqueline, HiiHilary, GreenallSameer A, JohnsTerrance G, GottardoNicholas G

EGFR inhibition
Extended survival (glioblastoma)
Antagonistic effects (medulloblastoma)

Dacomitinib, an EGFR pathway blocker, showed efficacy in glioblastoma and medulloblastoma in vitro and in vivo, but showed antagonism when combined with standard chemotherapies for medulloblastoma.

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.

The ERBB receptor inhibitor dacomitinib suppresses proliferation and invasion of pancreatic ductal adenocarcinoma cells.

Author: MomenyMajid, EsmaeiliFatemeh, HamzehlouSepideh, YousefiHassan, JavadikoosheshSepehr, VahdatiradVasimeh, AlishahiZivar, MousavipakSeyedeh H, BashashDavood, DehpourAhmad R, TavangarSeyyed M, Tavakkoly-BazzazJavad, HaddadPeiman, KordbachehFarzaneh, AlimoghaddamKamran, GhavamzadehArdeshir, GhaffariSeyed H

Anti-tumor activity

This study examined the anti-tumor activity of dacomitinib, a pan-ERBB receptor inhibitor, on pancreatic ductal adenocarcinoma (PDAC) cells. The ERBB family is overexpressed in PDAC and plays a role in tumorigenesis.

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

Language : English

22.

Front-line Therapy in Advanced Non-Small Cell Lung Cancer With Sensitive Epidermal Growth Factor Receptor Mutations: A Network Meta-analysis.

Author: LiXu-Yuan, LinJia-Zhou, YuShu-Han

Effective treatment

This article discusses the use of EGFR tyrosine kinase inhibitors (TKIs) in the treatment of non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation. While gefitinib and erlotinib are considered standard of care, TKI-based combination therapy is being investigated for its promising results.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

23.

Effects of secondary EGFR mutations on resistance against upfront osimertinib in cells with EGFR-activating mutations in vitro.

Author: NishinoMasaya, SudaKenichi, KobayashiYoshihisa, OharaShuta, FujinoToshio, KogaTakamasa, ChibaMasato, ShimojiMasaki, TomizawaKenji, TakemotoToshiki, MitsudomiTetsuya

EGFR-TKI treatment
Drug resistance

This study investigated whether resistance mutations that emerged with T790 M were responsible for the osimertinib resistance in the first-line setting.

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

24.

Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial.

Author: AiXinghao, SongZhengbo, JianHong, ZhouZhen, ChenZhiwei, YuYongfeng, LiZiming, LuShun

Treats HER2-mutant NSCLC
Diarrhea

Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. This article discusses the limitations of current treatment options and explores the potential of emerging therapies, such as trastuzumab deruxtecan, pyrotinib, and thalidomide, for treating HER2-mutant NSCLC. The article also addresses the challenges of pyrotinib-related diarrhea and highlights the potential of thalidomide in mitigating gastrointestinal toxicity.

Clinical Trial ProtocolA plan for conducting a clinical trial. It describes in detail the purpose, design, methodology, and statistical considerations of the trial, ensuring the transparency and consistency of the trial.
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.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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