Effects of brigatinib: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Main Research Findings

Brigatinib is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 Brigatinib has been shown to significantly prolong progression-free survival (PFS) and improve response rates compared to other ALK inhibitors. 19 Brigatinib has shown significant efficacy in treating patients with ALK-positive NSCLC, including those with brain metastases. 21 、 15 Brigatinib has been found to be effective in patients who have previously received treatment with other ALK inhibitors, such as crizotinib, alectinib, and ceritinib. 25 、 7 Brigatinib has been shown to be effective in treating ALK-positive NSCLC patients in various regions, including Latin America. 14 Brigatinib may be a potent inhibitor of ROS1, and may be effective in treating ROS1-rearranged NSCLC. 3 、 17 Brigatinib is generally well-tolerated, but it is important to be aware of potential side effects. 13 Brigatinib can cause interstitial lung disease (ILD). 11 Brigatinib can inhibit the activity of the organic cation transporter 3 (OCT3). 9 Brigatinib can cause autoimmune hepatitis. 18

Benefits and Risks

Benefit Summary

Brigatinib is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 Brigatinib has been shown to significantly prolong progression-free survival (PFS) and improve response rates compared to other ALK inhibitors. 19 Brigatinib has shown significant efficacy in treating patients with ALK-positive NSCLC, including those with brain metastases. 21 、 15 Brigatinib has been found to be effective in patients who have previously received treatment with other ALK inhibitors, such as crizotinib, alectinib, and ceritinib. 25 、 7 Brigatinib has been shown to be effective in treating ALK-positive NSCLC patients in various regions, including Latin America. 14

Risk Summary

Brigatinib can cause interstitial lung disease (ILD). 11 Brigatinib can inhibit the activity of the organic cation transporter 3 (OCT3). 9 Brigatinib can cause autoimmune hepatitis. 18

Comparison Between Studies

Commonalities Between Studies

Brigatinib is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 Brigatinib has been shown to significantly prolong progression-free survival (PFS) and improve response rates compared to other ALK inhibitors. 19

Differences Between Studies

Brigatinib has shown significant efficacy in treating patients with ALK-positive NSCLC, including those with brain metastases. 21 、 15 Brigatinib has been found to be effective in patients who have previously received treatment with other ALK inhibitors, such as crizotinib, alectinib, and ceritinib. 25 、 7 Brigatinib has been shown to be effective in treating ALK-positive NSCLC patients in various regions, including Latin America. 14 Brigatinib may be a potent inhibitor of ROS1, and may be effective in treating ROS1-rearranged NSCLC. 3 、 17

Consistency and Contradictions in Results

The research consistently shows that brigatinib is an effective treatment for ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 However, it is important to be aware of the potential side effects of brigatinib, such as interstitial lung disease (ILD), inhibition of the organic cation transporter 3 (OCT3), and autoimmune hepatitis. 11 9 18

Considerations for Real-World Application

Brigatinib is an effective treatment for ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 However, it is important to carefully consider the potential risks and benefits of this medication, and to monitor patients for any signs of side effects. 11 9 18

Limitations of Current Research

Further research is needed to better understand the effects of brigatinib, as the current body of research is still limited. 24 、 19 、 20 、 14

Future Research Directions

Future research should focus on finding ways to minimize the side effects of brigatinib and optimize its dosage and delivery methods. 11 9 18

Conclusion

Brigatinib is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). 24 、 19 、 20 、 14 It is important to weigh the risks and benefits of brigatinib carefully and to monitor patients for side effects. Further research is needed to minimize side effects and optimize brigatinib's dosage and delivery methods. 11 9 18

Literature analysis of 26 papers
Positive Content
23
Neutral Content
2
Negative Content
1
Article Type
1
3
1
8
24
1.

Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile.

Author: RenChaowei, SunNing, LiuHaixia, KongYing, SunRenhong, QiuXing, ChenJinju, LiYan, ZhangJianshui, ZhouYuedong, ZhongHui, YinQianqian, SongXiaoling, YangXiaobao, JiangBiao

Brigatinib
Cancer Treatment
PROTAC
SIAIS164018

SIAIS164018, a Brigatinib-derived degrader, exhibited unique features, including the ability to degrade ALK fusion proteins and mutant EGFR, key targets in non-small-cell lung cancer. It also inhibited cell migration and invasion and degraded several important oncoproteins involved in metastasis. Importantly, SIAIS164018 was orally bioavailable and well tolerated in vivo.

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

2.

Toxicity profile of anaplastic lymphoma kinase tyrosine kinase inhibitors for patients with non-small cell lung cancer: A systematic review and meta-analysis.

Author: TaoYunxia, ZhouYu, TangLe, ChenHaizhu, FengYu, ShiYuankai

NSCLC treatment
Drug toxicities

ALK inhibitors are drugs used to treat lung cancer that has a specific genetic change (ALK-positive). This meta-analysis examined the side effects of different ALK inhibitors. The study found that most patients experience at least one side effect, with the most common being gastrointestinal problems, liver enzyme elevation, and skin rash.

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.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Clinical activity of brigatinib in ROS1-rearranged non-small cell lung cancer.

Author: DudnikE, AgbaryaA, GrinbergR, CyjonA, BarJ, MoskovitzM, PeledN,

Cancer treatment

A study of 10 patients with ROS1-rearranged advanced non-small cell lung cancer (NSCLC) treated with brigatinib found that three patients demonstrated a partial response (ORR-37%). One crizotinib-naive patient had an ongoing response at 21.6 months. The drug demonstrated modest activity in crizotinib-resistant patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Cost‑Effectiveness of Lorlatinib in First-Line Treatment of Adult Patients with Anaplastic Lymphoma Kinase (ALK)‑Positive Non‑Small‑Cell Lung Cancer in Sweden.

Author: NaikJaesh, BeaversNorma, NilssonFredrik O L, IadelucaLaura, LowryChrissy

ALK+ NSCLC treatment

This study investigated the cost effectiveness of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), used first-line in Sweden to treat patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC).

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.

Language : English

5.

Sharing Experience with Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors in Lung Cancer: An Italian Expert Panel Discussion.

Author: GridelliCesare, TiseoMarcello, CortinovisDiego Luigi, MigliorinoMaria Rita, BarbieriVito, BironzoPaolo, BearzAlessandra, AttiliIlaria, de MarinisFilippo

Effective ALK TKI treatment
Improved survival
Varying clinical expertise

ALK tyrosine kinase inhibitors have revolutionized the treatment of ALK-positive non-small cell lung cancer, but different TKIs are available in different countries due to varying regulatory approvals. This article describes the different treatment scenarios and considerations for clinicians.

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.

Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human carcinoma A549 lung cell lines.

Author: AhmedMohammed Muqtader, FatimaFarhat, AnwerMd Khalid, AldawsariMohammed F, AlsaidanYasser Saud M, AlfaizSuliman Abdulaziz, HaqueAnzarul, AzAlanazi, AlhazzaniKhalid

Cancer treatment
Improved cytotoxicity
Sustained release

Brigatinib (BG) is a tyrosine kinase receptor inhibitor used to treat cancer. This study developed solid lipid nanoparticles (SLNs) loaded with BG to improve the drug's efficacy and reduce side effects. The study found that the optimized SLNs showed better cytotoxicity against lung cancer cells compared to BG suspension and blank SLNs.

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

7.

Real-World Efficacy and Tolerability of Brigatinib in Patients with Non-Small Cell Lung Cancer with Prior ALK-TKIs in the United States.

Author: JahanzebMohammad, LinHuamao M, WuYanyu, ZhangPingkuan, GorritzMagdaliz, McGuinessCatherine B, HuangWei-Ti, SunKainan, ChenChi-Chang, CamidgeD Ross

Effective treatment
Well tolerated
Dose reduction

This retrospective study evaluated real-world brigatinib use in ALK-rearranged non-small cell lung cancer (NSCLC) patients in the US who had previously received other ALK-TKIs. Brigatinib appeared to be effective and well-tolerated, with a median time to treatment discontinuation of 10.3 months. Adherence was high, and most patients achieved the target dose of 180 mg/day. Dose reductions were less frequent than in trials.

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.

Population Pharmacokinetics of Brigatinib in Healthy Volunteers and Patients With Cancer.

Author: GuptaNeeraj, WangXiaohui, OffmanElliot, ProhnMarita, NarasimhanNarayana, KersteinDavid, HanleyMichael J, VenkatakrishnanKarthik

Lung cancer treatment

This study presents a population pharmacokinetic model-based analysis for brigatinib, an oral tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer.

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

10.

Effects of Strong CYP2C8 or CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Brigatinib, an Oral Anaplastic Lymphoma Kinase Inhibitor, in Healthy Volunteers.

Author: TugnaitMeera, GuptaNeeraj, HanleyMichael J, SonnichsenDaryl, KersteinDavid, DorerDavid J, VenkatakrishnanKarthik, NarasimhanNarayana

CYP3A inducer interactions
CYP3A inhibitor interactions

This study investigates the effects of strong CYP3A inhibitors and inducers on the pharmacokinetics of brigatinib, an anaplastic lymphoma kinase inhibitor. Strong CYP3A inhibitors increased brigatinib exposure, while strong inducers reduced it significantly. CYP2C8 inhibition did not meaningfully affect brigatinib clearance.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
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

12.

Pharmacokinetic-Based Drug-Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review.

Author: ZhaoDehua, ChenJing, ChuMingming, LongXiaoqing, WangJisheng

Effective NSCLC treatment
Drug-drug interactions

This review summarizes the pharmacokinetic parameters and drug-drug interactions associated with ALK-TKIs to provide specific recommendations for oncologists and clinical pharmacists when prescribing ALK-TKIs.

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

15.

Treatment of brain metastases in ALK-positive non-small cell lung cancer.

Author: CeddiaSerena, Codacci-PisanelliGiovanni

ALK-inhibitors
Brain Metastases
Radiotherapy Toxicity

This abstract suggests that ALK-inhibitors may be a better first-line treatment option for patients with ALK-translocated non-small cell lung cancer (NSCLC) with brain metastases, as they offer longer survival with fewer side effects compared to radiotherapy.

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

17.

Emerging EGFR-Mutated Subclones in a Patient With Metastatic ALK-Rearranged Lung Adenocarcinoma Treated With ALK-Targeted Therapy: A Case Report.

Author: LeungJackson Ka Chun, KwokWang Chun, LeungArthur Chun Fung, TsuiPo, HoJames Chung-Man

ALK inhibitor resistance

This case report describes a patient with ALK-rearranged metastatic lung adenocarcinoma who initially responded to ALK inhibitors but later developed resistance due to the emergence of an EGFR L858R mutation. The patient ultimately achieved a very good partial response with erlotinib therapy.

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

20.

Brigatinib in Japanese patients with ALK-positive non-small-cell lung cancer: Final results of the phase 2 J-ALTA trial.

Author: YoshidaTatsuya, KumagaiToru, ToyozawaRyo, KatayamaRyohei, NishioMakoto, SetoTakashi, GotoKoichi, YamamotoNobuyuki, OheYuichiro, KudouKentarou, AsatoTakayuki, ZhangPingkuan, NakagawaKazuhiko

Duration of response
Improved PFS
ORR
Grade ≥3 adverse events

This study evaluated the efficacy and safety of brigatinib in Japanese patients with advanced ALK+ non-small-cell lung cancer (NSCLC). Brigatinib demonstrated effectiveness in both TKI-naive and TKI-pretreated patients, showing a significant improvement in progression-free survival and objective response rate. Brigatinib is an important treatment option for patients with ALK+ NSCLC, including those previously treated with other TKIs.

Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
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

21.

Brigatinib treated ALK positive lung squamous cell carcinoma after failed chemotherapy: A case report.

Author: LiShuluan, ZhangPei, WangTianyu, WangJie, DuanJianchun

ALK inhibitor
Brigatinib
Lung sqCC treatment

This case report describes the successful use of brigatinib, an anaplastic lymphoma kinase (ALK) inhibitor, in a patient with ALK-positive lung squamous cell carcinoma (sqCC). The patient achieved a response lasting approximately 11 months with tolerable side effects, suggesting that ALK inhibitors may be effective in ALK-positive sqCC.

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

22.

A Bayesian network meta-analysis of ALK inhibitor treatments in patients with ALK-positive non-small cell lung cancer.

Author: ZhengBei, JiangHong, YangWenjuan, LiYing, LiangBingqing, ZhuJun, ChenNanmei, ChenMiao, ZhangMeiling

ORR (alectinib)
ORR (lorlatinib)
PFS (alectinib)
PFS (lorlatinib)
Safety (alectinib)
Discontinuation (ceritinib)

Alectinib was the first choice for patients with ALK-positive non-small cell lung cancer (NSCLC), even for those with brain metastasis (BM), while lorlatinib was the second choice. Alectinib demonstrated the potentially best safety in terms of serious adverse events (SAEs), while lorlatinib had the longest progression-free survival (PFS) and PFS with BM.

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

24.

Alectinib for treating patients with metastatic <i>ALK</i>-positive NSCLC: systematic review and network metanalysis.

Author: Samacá-SamacáDaniel, Prieto-PintoLaura, PerézAndrés Yepes, ValderramaCarolina, HernándezFabián

Alectinib efficacy
Alectinib safety

This systematic literature review compared the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive non-small cell lung cancer. Alectinib reduced the risk of death and progression compared with crizotinib and ceritinib and had a good safety profile.

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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