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DRUG CLASS:

TrkC kinase inhibitor

2d
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)
3d
Enrollment change
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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) • ETV6 (ETS Variant Transcription Factor 6)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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Vitrakvi (larotrectinib)
3d
New trial • Real-world evidence • Real-world • Metastases
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Xalkori (crizotinib) • Rozlytrek (entrectinib)
4d
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)
24d
ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov)
P2, N=70, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025
Trial completion date
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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) • ETV6 (ETS Variant Transcription Factor 6)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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Vitrakvi (larotrectinib)
24d
Enrollment change • Metastases
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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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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • NTRK fusion
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Vitrakvi (larotrectinib)
25d
Larotrectinib to Enhance RAI Avidity in Differentiated Thyroid Cancer (clinicaltrials.gov)
P2, N=13, Recruiting, Children's Hospital of Philadelphia | Trial primary completion date: Oct 2024 --> Oct 2026
Trial primary completion date
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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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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion
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Vitrakvi (larotrectinib)
26d
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)
1m
Enrollment change • Trial completion date
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib)
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
A pilocytic astrocytoma with novel ATG16L1::NTRK2 fusion responsive to larotrectinib: a case report with genomic and functional analysis. (PubMed, Oncologist)
Presently, after 22 months of treatment, the patient's complete remission is sustained. Our findings highlight the importance of screening for other oncogenic drivers in BRAF-negative LGGs since rare fusion genes may serve as targets for precision oncology therapy.
Journal
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BRAF (B-raf proto-oncogene) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TYK2 (Tyrosine Kinase 2) • NTRK (Neurotrophic receptor tyrosine kinase) • ATG16L1 (Autophagy Related 16 Like 1)
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NTRK2 fusion • NTRK fusion
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Vitrakvi (larotrectinib)
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
Secretory Carcinoma of the Thyroid: A Case Report and Update of Literature. (PubMed, Head Neck Pathol)
Among documented cases of thyroid SC, prognostic factors established for salivary SC have shown broad distributions, including a mitotic activity ranging from < 1 to 10 per 10 high-power fields and variable presence of necrosis, awaiting additional case experience to better elucidate their relevance in thyroid SC. We hereby present a 61-year-old female patient with widely metastatic thyroid SC treated with larotrectinib and provide an updated review of the literature on the molecular pathogenesis and clinicopathologic characteristics of this rare entity.
Review • Journal
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • PAX8 (Paired box 8)
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NTRK3 fusion
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Vitrakvi (larotrectinib)
2ms
Single-Institution Experience of Larotrectinib Therapy for Patients With NTRK Fusion-Positive Thyroid Carcinoma. (PubMed, J Endocr Soc)
Patients achieved 1 complete response (12%), 6 partial responses (75%), and 1 stable disease (12%). In this single-institution cohort of patients with NTRK fusion-positive thyroid cancer, NTRK inhibition led to an mPFS of 25 months, with survival surpassing historic benchmarks for ATC and PDTC.
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK positive • NTRK fusion
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Vitrakvi (larotrectinib)
2ms
Application of newly developed and validated UPLC-MS/MS method for pharmacokinetic study of ROS1/NTRK inhibitor taletrectinib in beagle dog plasma. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci)
The procedure was then applied to quantify taletrectinib in beagle dog plasma after oral and intravenous doses and achieved success. The obtained pharmacokinetic parameters indicated high bioavailability of taletrectinib (>85 %) and extensive tissue distribution (>40 L/kg).
PK/PD data • Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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taletrectinib (AB-106)
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)
2ms
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)
2ms
Nerve growth factor promote VCAM-1-dependent monocyte adhesion and M2 polarization in osteosarcoma microenvironment: Implications for larotrectinib therapy. (PubMed, Int J Biol Sci)
In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.
Journal
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VCAM1 (Vascular Cell Adhesion Molecule 1)
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Vitrakvi (larotrectinib)
3ms
Long-Term Tumor Stability After First-Line Treatment With Larotrectinib in an Infant With NTRK2 Fusion-Positive High-Grade Glioma. (PubMed, J Natl Compr Canc Netw)
Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.
Journal
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK2 fusion • ALK fusion • ROS1 fusion • MET fusion • NTRK positive • NTRK fusion
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Vitrakvi (larotrectinib) • 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)
|
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)
|
Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
New P3 trial • Metastases
|
Xalkori (crizotinib) • taletrectinib (AB-106)
3ms
Trial primary completion date • Metastases
|
NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
|
Vitrakvi (larotrectinib)
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
|
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)
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
4ms
New P2 trial
|
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)
|
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
4ms
Larotrectinib efficacy for liver metastases in papillary thyroid carcinoma patient harboring SQSTM1-NTRK1 fusion. (PubMed, Surg Case Rep)
In conclusion, larotrectinib demonstrated effective antitumor activity against liver metastases of PTC, a relatively rare site of distant metastasis. Furthermore, the efficacy of larotrectinib was maintained, even though the patient had a history of multi-tyrosine kinase inhibitor treatment and a relatively infrequent fusion gene, SQSTM1-NTRK1.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • SQSTM1 (Sequestosome 1) • NTRK (Neurotrophic receptor tyrosine kinase)
|
OncoGuide™ NCC Oncopanel System
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Vitrakvi (larotrectinib) • Lenvima (lenvatinib)
4ms
Poor outcome in congenital mesoblastic nephroma with TPM3::NTRK1 fusion: a case report from multi-disciplinary treatment to molecular tumor board. (PubMed, Transl Pediatr)
CMN, is a rare pediatric renal tumor that warrant prompt surgical management. A watchful waiting approach may allow for aggressive growth of metastatic disease, as seen in this case of cellular CMN with TPM3::NTRK1 fusion gene, TRK inhibitors can play significant roles in the treatment of CMN with TPM3::NTRK1 fusion gene, but we still need to pay attention to the phenomenon of drug resistance to larotrectinib caused by site mutations of TRKA.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3)
|
Vitrakvi (larotrectinib)
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)
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
Journal
|
ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
taletrectinib (AB-106)
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
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Lynparza (olaparib) • carboplatin • gemcitabine • 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)
|
PD-L1 IHC 22C3 pharmDx
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Vitrakvi (larotrectinib) • 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)