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DRUG CLASS:

TNK2 inhibitor

5d
Young-Onset, ROS1-Rearranged Adenocarcinoma of the Lung With Cardiac Tamponade: A Case Report. (PubMed, Cureus)
Oral administration of entrectinib was highly effective, and his serum carcinoembryonic antigen (CEA) level improved from 247 to 10.8 ng/mL. The present case has clinical significance because a pathological and genetic diagnosis was made from the pericardial effusion fluid, and the clinical manifestations of cardiac tamponade due to lung cancer were well controlled by the administration of entrectinib.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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ROS1 rearrangement
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Rozlytrek (entrectinib)
5d
New trial • Real-world evidence • Real-world • Metastases
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Xalkori (crizotinib) • Rozlytrek (entrectinib)
6d
Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison. (PubMed, Lung Cancer)
The outcomes in this MAIC study including Asian patients with ROS1-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 positive
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Xalkori (crizotinib) • Rozlytrek (entrectinib)
29d
Gene-expression profile analysis to disclose diagnostics and therapeutics biomarkers for thyroid carcinoma. (PubMed, Comput Biol Chem)
Then we detected 6 repurposable drug molecules (Entrectinib, Imatinib, Ponatinib, Sorafenib, Retevmo, and Pazopanib) by molecular docking with KGs-mediated receptor proteins, ADME/T analysis, and cross-validation with the independent receptors. Therefore, these findings might be useful resources for wet lab researchers and clinicians to consider an effective treatment strategy against THCA.
Journal • Gene Expression Profile
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TOP2A (DNA topoisomerase 2-alpha) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • RUNX2 (RUNX Family Transcription Factor 2)
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KIM1 expression • TIMP1 expression
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sorafenib • Rozlytrek (entrectinib) • imatinib • Iclusig (ponatinib) • pazopanib • Retevmo (selpercatinib)
1m
Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions. (PubMed, Cancers (Basel))
Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases...More recently, the FDA approved the use of repotrectinib, a second-generation TRK inhibitor, in patients with NTRK fusions, based on data suggesting clinical efficacy and safety, which could offer another tool for the treatment of NTRK-altered cancers. In this review, we summarize the current evidence related to the use of TRK inhibitors in the tissue-agnostic setting. We also elaborate on the safety profiles and resistance mechanisms from a practical perspective.
Review • Journal • Pan tumor
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
2ms
Response to Crizotinib After Entrectinib Resistance in ROS1-Rearranged, MET-Amplified Lung Adenocarcinoma. (PubMed, JCO Precis Oncol)
Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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MET amplification • ROS1 rearrangement • ROS1 amplification
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Xalkori (crizotinib) • Rozlytrek (entrectinib)
2ms
RACK1 inhibits ferroptosis of cervical cancer by enhancing SLC7A11 core-fucosylation. (PubMed, Glycoconj J)
Mechanistically, RACK1 increased the expression of FUT8 by inhibiting miR-1275, which in turn promoted the FUT8-catalyzed core-fucosylation of cystine/glutamate antiporter SLC7A11, thereby inhibiting SLC7A11 degradation and cell ferroptosis. Our data highlight the role of RACK1 in cervical cancer progression and its suppression of ferroptosis via the RACK1/miR-1275/FUT8/SLC7A11 axis, suggesting that inhibiting this pathway may be a promising therapeutic approach for patients with cervical cancer.
Journal
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SLC7A11 (Solute Carrier Family 7 Member 11) • FUT8 (Fucosyltransferase 8) • MIR127 (MicroRNA 127) • RACK1 (Receptor For Activated C Kinase 1)
2ms
Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial. (PubMed, Target Oncol)
In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.
Retrospective data • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK positive • NTRK fusion
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Rozlytrek (entrectinib)
2ms
Current Landscape of NTRK Inhibition for Pediatric CNS Tumors. (PubMed, CNS Drugs)
The use of larotrectinib and entrectinib in the relapsed setting for pediatric CNS tumors has resulted in rapid and robust responses in an important fraction of patients. As these agents are more broadly used, resistance will become a more pervasive issue and strategies will need to be determined for this scenario. This article summarizes the current status of NTRK inhibitors for pediatric CNS tumors and discusses the opportunities and challenges of their expanding use in the future.
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK positive • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
2ms
ROS1-rearranged non-small cell lung cancer: Understanding biology and optimizing management in the era of new approvals. (PubMed, Curr Probl Cancer)
Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.
Review • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
2ms
Unusual presentation of ROS1 rearranged metastatic non-small cell lung cancer. (PubMed, Respir Med Case Rep)
The patient was ultimately diagnosed with ROS1 rearranged lung adenocarcinoma and achieved a dramatic response with entrectinib. This case highlights the variable presentation of non-small cell lung cancer (NSCLC) and the importance of comprehensive molecular testing for newly diagnosed metastatic NSCLC.
Journal • Metastases
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Rozlytrek (entrectinib)
3ms
Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-type Non-Small Cell Lung Cancer. (PubMed, Cancer Res)
Notably, suppression of the NTRK1 pathway by knockdown or Entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models...RNA sequencing revealed that suppression of NTRK1 signaling in tumor cells increased complement C3 expression, which enhanced the recruitment of T cells and myeloid cells and stimulated M1-like macrophage polarization in the tumor. Together, this study demonstrates a role for NTRK1 signaling in regulating crosstalk between tumor cells and immune cells in the tumor microenvironment and provides a potential therapeutic approach to overcomes immunotherapy resistance in NTRK1 wild-type NSCLC patients.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
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Rozlytrek (entrectinib)
3ms
Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study). (PubMed, Curr Oncol)
Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.
Retrospective data • Journal • Real-world evidence • Real-world
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
Advances and future directions in ROS1 fusion-positive lung cancer. (PubMed, Oncologist)
The preferred Food and Drug Administration-approved first-line therapies include crizotinib, entrectinib, and repotrectinib, and currently, selection amongst these options requires consideration of the systemic and CNS efficacy, tolerability, and access to therapy. Herein, we describe a practical approach for the selection of initial and subsequent therapies for metastatic ROS1+ NSCLC based on these clinical considerations. Additionally, we explore the evolving evidence for the optimal treatment of earlier-stage, non-metastatic ROS1+ NSCLC, while, in parallel, highlighting future research directions with the goal of continuing to build on the tremendous progress in the management of ROS1+ NSCLC and ultimately improving the longevity and well-being of people living with this disease.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
CRAFT: Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors (clinicaltrials.gov)
P2, N=52, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting
Enrollment open
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carboplatin • Rozlytrek (entrectinib) • cyclophosphamide • etoposide IV • Neulasta (pegfilgrastim) • Neupogen (filgrastim)
4ms
Identification of Key Genes and Signaling Pathways in Entrectinibresistant Non-small Cell Lung Cancer Using Bioinformatic Analysis and Experimental Verification. (PubMed, Curr Med Chem)
We have identified core genes associated with non-small cell resistance to entrectinib, including CHI3L2, ZEB2, and S100A12. ZEB2 is a core gene associated with acquired resistance to entetinib in NSCLC.
Journal
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CELF2 (CUGBP Elav-Like Family Member 2) • PDK4 (Pyruvate Dehydrogenase Kinase 4) • MIR1293 (MicroRNA 1293) • SEMA5A (semaphorin 5A) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2) • S100A12 (S100 Calcium Binding Protein A12)
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Rozlytrek (entrectinib)
4ms
The landscape of cancer-associated transcript fusions in adult brain tumors: a longitudinal assessment in 140 patients with cerebral gliomas and brain metastases. (PubMed, Front Oncol)
This study provides data on the incidence of NTRK gene fusions in brain tumors, which could strongly support the relevance of innovative clinical trials with specific targeted therapies (larotrectinib, entrectinib) in this population of patients. FGFR3 (17)::TACC3 (11) rearrangement was detected in breast carcinoma BM with the possibility of using some specific targeted therapies and TMPRSS (2)::ERG (4) rearrangements occur in a subset of patients with, prostatic carcinoma BM, endometrium BM, and oligodendroglioma (grade II), IDH-mutated and 1p19q co-deleted, where there are yet no approved ERG-directed therapies.
Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TACC3 (Transforming acidic coiled-coil containing protein 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
4ms
New P2 trial
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carboplatin • Rozlytrek (entrectinib) • cyclophosphamide • etoposide IV • Neulasta (pegfilgrastim) • Neupogen (filgrastim)
4ms
TRKing down drug resistance in NTRK fusion-positive cancers†. (PubMed, J Pathol)
Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents.
Journal
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NF2 (Neurofibromin 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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Rozlytrek (entrectinib)
4ms
Discovery of novel indazole derivatives as second-generation TRK inhibitors. (PubMed, Eur J Med Chem)
NTRK fusion-positive cancers can be treated with the first-generation TRK inhibitors, larotrectinib and entrectinib...And the inhibitory effect against TRKAG667C (IC50 = 9.9 nM) was better than that of selitrectinib (IC50 = 113.1 nM). Further, compound B31 exhibited moderate kinase selectivity and excellent plasma stability (t1/2 > 480 min). In vivo pharmacokinetic studies in Sprague-Dawley rats showed that B31 had acceptable pharmacokinetic properties.
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • selitrectinib (BAY 2731954)
4ms
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors. (PubMed, Acta Neuropathol Commun)
Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.
Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MDM4 (The mouse double minute 4) • TPM3 (Tropomyosin 3) • TFG (Trafficking From ER To Golgi Regulator) • FKBP15 (FKBP Prolyl Isomerase 15) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like) • GKAP1 (G Kinase Anchoring Protein 1) • KIF5A (Kinesin Family Member 5A)
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carboplatin • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib) • thiotepa
5ms
Efficacy and safety of NTRK inhibitors in patients with NTRK fusion-positive lung and thyroid cancers. (PubMed, Clin Adv Hematol Oncol)
Larotrectinib and entrectinib also produce robust and durable responses in NTRK fusion-positive thyroid cancer that is refractory to radioactive iodine. Second-generation TRK inhibitors that have been designed to overcome acquired resistance are under investigation.
Review • Journal • IO biomarker
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NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers. (PubMed, J Manag Care Spec Pharm)
Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.
Retrospective data • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
A case of breast secretory carcinoma metastasis to the lung in which NTRK fusion gene was confirmed by cancer genome profiling (JBCS 2024)
Currently, two drugs, entrectinib and larotrectinib, are approved for use in Japan, and they are planned to be used in this case in the event of recurrence. &lsqb;Summary] Cancer genome profiling was performed on a very rare case of lung metastasis from breast secretory carcinoma, and the ETV6-NTRK fusion gene was confirmed
Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
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PD-L1 IHC 22C3 pharmDx
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
Current status of gene panel testing in our department and a case report (JBCS 2024)
Gemcitabine+Carboplatin therapy was administered while waiting for the test results to come out, and it was highly effective. In such a situation, for patients with NTRK fusion genes, which are companion diagnostics for Entrectinib, and PALB2 gene mutations, which are suggested to be sensitive to Olaparib, early use of CGP testing contributes to improving prognosis, so the significance of early implementation of CGP testing is also being questioned. In one case experienced in our department, it is possible that better Carboplatin response and Olaparib sensitivity could have been maintained if CGP had been performed early
Clinical • Case report • PARP Biomarker • BRCA Biomarker • BRCA Companion diagnostic • PARP Companion diagnostic
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRACAnalysis CDx™ • FoundationOne® Liquid CDx
|
Lynparza (olaparib) • carboplatin • gemcitabine • Rozlytrek (entrectinib)
5ms
Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial. (PubMed, Nat Med)
The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 .
P2/3 data • Journal • Metastases
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Rozlytrek (entrectinib)
5ms
Repurposing FDA-approved compounds to target JAK2 for colon cancer treatment. (PubMed, Discov Oncol)
Our results indicated that ergotamine, entrectinib, exatecan, dihydroergotamine, and paritaprevir can be used as alternative drugs for colon cancer. The long-term inhibitory effect of the ergotamine led to a decrease in colony size, and the toxicity properties were studied using hemolysis assay. Our study shows the potential of targeting JAK2 as a novel approach to colon cancer treatment, and demonstrate that ergotamine as a promising effects as an anti-cancer drug.
FDA event • Journal
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IL6 (Interleukin 6)
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Rozlytrek (entrectinib)
5ms
Neoadjuvant Study of Targeting ROS1 in Combination With Endocrine Therapy in Invasive Lobular Carcinoma of the Breast (ROSALINE) (clinicaltrials.gov)
P2, N=65, Active, not recruiting, Jules Bordet Institute | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Apr 2024 --> Aug 2024
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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Rozlytrek (entrectinib) • letrozole • goserelin acetate
6ms
Dual Inhibition of the TrkA and JAK2 pathways using Entrectinib and Pacritinib suppresses the growth and metastasis of HER2-positive and triple-negative breast cancers. (PubMed, Cancer Lett)
Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells...The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • SOX2
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Herceptin (trastuzumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jakafi (ruxolitinib) • Vonjo (pacritinib)
6ms
Serial Cell-Free DNA Sequencing in ROS1 Fusion-Positive Lung Cancers During Treatment With Entrectinib. (PubMed, JCO Precis Oncol)
P2; Serial cfDNA monitoring may complement radiographic assessments as determinants of response and resistance to entrectinib in ROS1 fusion-positive lung cancers in addition to detecting putative resistance mechanisms on progression.
Journal • P2 data
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TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • CDH1 (Cadherin 1)
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MSK-ACCESS
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Rozlytrek (entrectinib)
6ms
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Rozlytrek (entrectinib)
6ms
Healthcare decision-making for tumour-agnostic therapies in Europe: lessons learned. (PubMed, Drug Discov Today)
The tumour-agnostic authorisations of larotrectinib and entrectinib shifted the paradigm for indication setting. These differences indicate difficulties experienced in these assessments and provide valuable lessons for future disruptive therapies. As we discuss here, early multistakeholder dialogues concerning minimum evidence requirements and involving clinicians are essential.
Review • Journal • Pan tumor
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NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
6ms
Pharmacological inhibition of PDGF-C/neuropilin-1 interaction: A novel strategy to reduce melanoma metastatic potential. (PubMed, Biomed Pharmacother)
Among the top 45 candidates with the highest affinity, five drugs were selected based on the safety profile, lack of hormonal effects, and current availability in the market: the antipsychotic pimozide, antidiabetic gliclazide, antiallergic cromolyn sodium, anticancer tyrosine kinase inhibitor entrectinib, and antihistamine azelastine. Both drugs also reverted PDGF-C ability to stimulate extracellular matrix invasion by melanoma cells resistant to BRAF inhibitors. The inhibitory effect on tumor cell motility involved a decrease of p130Cas phosphorylation, a signal transduction pathway activated by PDGF-C-mediated stimulation of NRP-1.
Journal • Metastases
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NRP1 (Neuropilin 1) • PDGFC (Platelet Derived Growth Factor C)
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Rozlytrek (entrectinib)
7ms
Entrectinib as first-line vs. second-line therapy in ROS1 fusion-positive non-small cell lung cancer: a cost-effectiveness analysis. (PubMed, Transl Lung Cancer Res)
Considering the current pricing of entrectinib, it is not deemed cost-effective as a first-line or second-line therapy for patients with ROS1 fusion-positive advanced NSCLC when compared to chemotherapy. Alternatively, reserving entrectinib exclusively for second-line therapy might strike a balance between healthcare expenditures and patient outcomes.
Journal • HEOR • Cost-effectiveness • Cost effectiveness
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 fusion • ROS1 positive
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Rozlytrek (entrectinib)
7ms
NTRK gene fusion testing and management in lung cancer. (PubMed, Cancer Treat Rev)
Larotrectinib and entrectinib are first-generation TRK inhibitors that have demonstrated efficacy in patients with TRK fusion lung cancers. Among these assays, RNA-based next-generation sequencing (NGS) can be considered a gold standard for detecting NTRK gene fusions; however, several alternatives with minimally acceptable sensitivity and specificity are also available in areas where widespread access to NGS is unfeasible. This review highlights the importance of testing for NTRK gene fusions in lung cancer, ideally using the gold-standard method of RNA-based NGS, the various assays that are available, and treatment algorithms for patients.
Review • Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
7ms
Inhibition of Human UDP-Glucuronosyltransferase Enzyme by Entrectinib: Implications for Drug-Drug Interactions. (PubMed, Chem Biol Interact)
Furthermore, the results from quantitative prediction research suggested that the combination of entrectinib at 600 mg/day with substrates primarily metabolized by hepatic UGT2B15 or intestinal UGT1A7 and UGT1A8 might cause clinical DDIs. Thus, special attention should be paid to avoid adverse reactions induced by DDIs when co-administration of entrectinib and drugs metabolized by UGTs.
Journal
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UGT1A7 (UDP Glucuronosyltransferase Family 1 Member A7) • UGT2B15 (UDP Glucuronosyltransferase Family 2 Member B15) • UGT1A8 (UDP Glucuronosyltransferase Family 1 Member A8)
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Rozlytrek (entrectinib)
7ms
Current Status and Issues of Companion Diagnostics in Cancer Genomic Medicine (PubMed, Gan To Kagaku Ryoho)
On the other hand, there are some approved drugs, such as pembrolizumab for TMB-H or entrectinib or larotrectinib for NTRK fusion gene, for which there is no stand-alone companion diagnostics and the eligibility for these drugs cannot be judged without the results of CGP test. This paper discusses the current status and issues of companion diagnostics in cancer genomic medicine.
Journal • Tumor mutational burden • Companion diagnostic • PD(L)-1 Biomarker • PD(L)-1 companion diagnostic
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TMB (Tumor Mutational Burden) • NTRK (Neurotrophic receptor tyrosine kinase)
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TMB-H • NTRK fusion
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Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
7ms
ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review. (PubMed, Int J Mol Sci)
The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.
Clinical • Observational data • Retrospective data • Review • Journal • IO biomarker • Stroma
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TFG (Trafficking From ER To Golgi Regulator) • NTRK (Neurotrophic receptor tyrosine kinase) • ANO1 (Anoctamin 1)
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NTRK3 fusion • RB1 mutation • PDGFRA mutation • NTRK3 positive • NTRK fusion
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Rozlytrek (entrectinib)
7ms
Preclinical • Journal
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NF2 (Neurofibromin 2) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NF2 mutation • NTRK fusion
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Mekinist (trametinib) • Rozlytrek (entrectinib) • sirolimus
8ms
ETV6-NTRK2 Fusion in a Patient With Metastatic Pulmonary Atypical Carcinoid Successfully Treated With Entrectinib: A Case Report and Review of the Literature. (PubMed, Clin Lung Cancer)
After pursuing other alternative treatments, including chemotherapy (ie, carboplatin, etoposide, capecitabine, temozolomide, and paclitaxel), everolimus, and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. To date, she has maintained sustained benefit for at least 1 year from initiation of entrectinib. Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.
Review • Journal • PD(L)-1 Biomarker • Metastases
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NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • SSTR (Somatostatin Receptor) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK2 fusion • ETV6-NTRK2 fusion • NTRK positive • SSTR Expression
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Tecentriq (atezolizumab) • carboplatin • Rozlytrek (entrectinib) • paclitaxel • everolimus • temozolomide • capecitabine • etoposide IV
8ms
Lung adenocarcinoma patients with ROS1-rearranged tumors by sex and smoking intensity. (PubMed, Heliyon)
Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.
Journal
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Lorbrena (lorlatinib)