Vitrakvi (larotrectinib) / Bayer, Pfizer - LARVOL DELTA

Cost-effectiveness analysis of larotrectinib vs standard of care for treatment of metastatic NTRK fusion colorectal cancer. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "The ICER of larotrectinib therapy vs regorafenib therapy or larotrectinib therapy vs trifluridine/tipiracil therapy was calculated at 23,321.46 USD/QALY or 22,585.39 USD/QALY. From the perspective of healthcare payers in China, larotrectinib was cost-effective compared to standard of care as a second-line treatment or subsequent treatment for advanced or metastatic CRC patients with NTRK gene fusion-positive."

HEOR • Journal • Colorectal Cancer • Oncology • Solid Tumor • NTRK

KRAS-Wild Pancreatic Cancer-More Targets than Treatment Possibilities? (PubMed, Cancers (Basel)) - "Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ALK • FGFR • KRAS • NRG1 • NTRK • RET • ROS1

Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions. (PubMed, Oncol Res) - "The purpose of this review is to explore the impact, safety, and challenges of tissue-agnostic therapies including pembrolizumab, dostarlimab, larotrectinib, entrectinib, repotrectinib, dabrafenib plus trametinib, selpercatinib, and trastuzumab deruxtecan. We discuss emergence of pan-histological biomarkers, such as neoantigen burden, current updates on trials as well as trial outlining strategies to refining patient selection, while also supporting broader access to biomarker testing. Collectively, these insights underscore the transformative role of tissue-agnostic therapies in precision oncology while emphasizing the ongoing need for research to optimize their application and overcome current barriers."

Biomarker • Journal • Pan tumor • Review • Oncology

Emerging Targeted Therapies and Ongoing Clinical Trials in Pediatric Brain Tumors (PubMed, No Shinkei Geka) - "Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus..."

Journal • Review • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • High Grade Glioma • Neurofibromatosis • Oncology • Pediatrics • Solid Tumor • BRAF • KIAA1549 • NF1 • NTRK

Beyond DNA: Two Pediatric Glioma Cases Highlight the Diagnostic and Therapeutic Impact of RNA Sequencing (SNO 2025) - "By then, the patient had already started selumetinib with a positive clinical response...This guided treatment with larotrectinib, which has been well tolerated and has led to sustained disease control for over two years without recurrence...Early integration of RNA testing alongside DNA profiling should be standard in pediatric neuro-oncology workflows to expand therapeutic options and enhance treatment precision. Larger cohort studies are underway to validate these findings and optimize RNA-driven decision-making in pediatric CNS tumors."

Clinical • Astrocytoma • Brain Cancer • CNS Tumor • Gene Therapies • Glioma • Pediatrics • Pilocytic Astrocytoma • Pleomorphic Xanthoastrocytoma • Solid Tumor • BRAF • CDKN2A • CDKN2B • KANK1 • KIAA1549 • MTAP • NTRK2

Next-Generation Targeted Therapy: The Evolving Role of Taletrectinib in Fusion-Positive Malignancies. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK • ROS1

Experts Unpack the Most Notable NCCN Guideline Changes Heading Into 2026 (OncLive) - "'[During 2025], adjuvant therapy regimens from the [phase 3] ATOMIC trial [NCT02912559]—FOLFOX or CAPEOX in combination with atezolizumab—were added in stage III dMMR/MSI-H colon cancer. This change represents the addition of checkpoint inhibitor therapies at earlier points of the patient journey.' Al B. Benson, III, MD...said in a statement to OncLive."

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Rare but not forgotten: Therapeutic advancements for rare childhood cancers. (PubMed, Mol Ther Oncol) - "This includes work that led to the FDA approvals of immune checkpoint inhibitors in multiple rare pediatric tumor types, the NTRK inhibitors larotrectinib, entrectinib, and repotrectinib for children and adults with solid tumors with NTRK fusions, the ALK inhibitor crizotinib in children and adults with ALK-positive inflammatory myofibroblastic tumors, and the radioligand LUATHERA for adolescents and adults with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Despite these advances, the study of rare pediatric cancers faces multiple challenges including a limited number of patients for efficient and well-powered clinical trials and a dearth of financial incentives. Ongoing, coordinated efforts are needed to continue the advancement of novel treatments and improve survival and minimize late effects."

Journal • Review • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pediatrics • Sarcoma • Solid Tumor • NTRK • SSTR

Surgical resection and targeted therapy in a pediatric NTRK-rearranged low-grade spindle cell sarcoma: a case report. (PubMed, Childs Nerv Syst) - "This case underscores the importance of integrating molecular diagnostics into the evaluation of atypical spindle cell tumors, particularly those presenting with aggressive clinical features despite low-grade histology. Early identification of NTRK fusions enables timely initiation of TRK inhibitor therapy, offering durable disease control and functional recovery. Broader awareness and implementation of molecular testing can greatly enhance the management of rare pediatric sarcomas."

Journal • CNS Disorders • Fibrosis • Oncology • Pediatrics • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Spindle Cell Sarcoma • CD34 • NTRK • NTRK1 • TPM3

ADVL1823: Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Mar 2026 ➔ Jul 2027

Trial completion date • Brain Cancer • CNS Tumor • Fibrosarcoma • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Sarcoma • Solid Tumor • ETV6 • NTRK1 • NTRK2 • NTRK3

Agnostic Biomarkers in Molecular Pathology. (PubMed, J Clin Pract Res) - "The United States Food and Drug Administration (FDA) has approved pembrolizumab for MSI-high tumors or tumors with a high TMB. Larotrectinib and entrectinib have been approved for the treatment of NTRK gene fusion-positive tumors. Additionally, the combination of dabrafenib and trametinib has been approved for BRAF V600E mutations, and selpercatinib has been approved for RET fusion-positive cancers as of 2022. Positive responses to agnostic therapy, a significant milestone in cancer treatment, depend on the identification of new agnostic biomarkers. Ongoing research is focused on defining additional molecular changes, such as programmed death-ligand 1 (PD-L1), Kirsten rat sarcoma virus (KRAS), neuregulin 1 (NRG1), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK), AKT serine/threonine kinase (AKT), human epidermal growth factor receptor 2 (HER2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and breast cancer..."

Biomarker • IO biomarker • Journal • Review • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Microsatellite Instability • Oncology • Sarcoma • Solid Tumor • ALK • BRAF • BRCA • FGFR • HER-2 • KRAS • MSI • NRG1 • NTRK • PD-L1 • PIK3CA • RET • TMB

Identification of a novel PRUNE2::NTRK2 gene fusion in soft tissue sarcoma patients-friend or foe? Case series. (PubMed, Ther Adv Med Oncol) - "Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected."

Journal • Colorectal Cancer • Genito-urinary Cancer • Neuroblastoma • Oncology • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NTRK • NTRK2

Larotrectinib for NTRK amplification in glioblastoma: Case report (SNO 2025) - "He underwent complete resection of the dominant lesion followed by concurrent temozolomide with radiation and 6 cycles of adjuvant temozolomide as well as tumor treating fields...Larotrectinib was discontinued and third line treatment with lomustine and bevacizumab was initiated...Our patient with glioblastoma harboring NTRK2 gene amplification did not have response to larotrectinib. Larotrectinib has demonstrated efficacy in gliomas with NRTK fusions but may not have efficacy in gliomas with NRTK amplifications."

Case report • Clinical • Brain Cancer • CNS Tumor • Esophageal Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor • MGMT • NTRK • NTRK1 • NTRK2

Beyond DNA: Two Pediatric Glioma Cases Highlight the Diagnostic and Therapeutic Impact of RNA Sequencing (WFNOS 2025) - "By then, the patient had already started selumetinib with a positive clinical response...This guided treatment with larotrectinib, which has been well tolerated and has led to sustained disease control for over two years without recurrence...Early integration of RNA testing alongside DNA profiling should be standard in pediatric neuro-oncology workflows to expand therapeutic options and enhance treatment precision. Larger cohort studies are underway to validate these findings and optimize RNA-driven decision-making in pediatric CNS tumors."

Clinical • Astrocytoma • Brain Cancer • CNS Tumor • Gene Therapies • Glioma • Pediatrics • Pilocytic Astrocytoma • Pleomorphic Xanthoastrocytoma • Solid Tumor • BRAF • CDKN2A • CDKN2B • KANK1 • KIAA1549 • MTAP • NTRK2

TPM3-NTRK1 Fusion Cervical Sarcoma: A Case Report of a Novel Subset of Gynaecological Sarcomas and Successful Treatment of Recurrent Disease With Trk-Inhibition Therapy. (PubMed, Cureus) - "The patient remains stable with no evidence of local, nodal, or metastatic disease for more than three years following the initial presentation. This report aims to propose the use of larotrectinib as a management option for recurrent NTRK-positive cervical sarcomas."

Journal • Gynecologic Cancers • Oncology • Sarcoma • Solid Tumor • NTRK • NTRK1 • TPM3

PROSPECTIVE REAL-WORLD STUDY OF LAROTRECTINIB (LARO) IN PATIENTS (PTS) WITH TRK FUSION SOLID TUMORS: INTERIM ANALYSIS OF ON-TRK (CTOS 2025) - P | "Laro demonstrated manageable safety and favorable response rates and survival in a prospective, real-world trial.Table"

Clinical • Real-world • Real-world evidence • Brain Cancer • CNS Tumor • Fibrosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NTRK

FUSION GENES IN SARCOMAS: DIAGNOSTIC APPROACHES AND EMERGING TARGETED THERAPIES (CTOS 2025) - "Tyrosine Kinase Fusions, including NTRK, ALK, COL1A1-PDGFB, are highly actionable with FDA-approved therapies like larotrectinib and imatinib.3. Fusion genes are central to sarcoma diagnosis and treatment. They are a key to transforming and personalizing sarcoma management. Barriers in this path include the rarity of fusions, limited actionability, and lack of comprehensive fusion registries."

IO biomarker • Oncology • Sarcoma • Solid Tumor • ALK • BCOR • COL1A1 • DUX4 • EWSR1 • FLI1 • NAB2 • NTRK • PAX3 • PDGFB • SS18 • STAT6 • TFE3 • YAP1

A SYSTEMATIC REVIEW OF FUSION-DRIVEN SARCOMAS (CTOS 2025) - "Tyrosine Kinase Fusions including NTRK, ALK, and COL1A1-PDGFB are highly actionable with FDA-approved therapies like larotrectinib, imatinib, and others. With the continued discovery of tumor-specific oncogenes, understanding fusion protein activity is essential for developing efficacious systemic therapies. Barriers in this path include the rarity of fusions, limited actionability, and lack of comprehensive fusion registries. Our proposed systematic review aims to assess the evolving clinical utility of fusion-targeted diagnostics and therapies."

IO biomarker • Review • Oncology • Sarcoma • Solid Tumor • ALK • BCOR • COL1A1 • DUX4 • EWSR1 • FLI1 • NAB2 • NTRK • PAX3 • PDGFB • SS18 • TFE3 • YAP1

EFFICACY AND SAFETY OF LAROTRECTINIB (LARO) IN PATIENTS (PTS) WITH TRK FUSION SARCOMAS (CTOS 2025) - P1, P1/2, P2 | "Laro shows durable long-term responses and manageable safety in pts with TRK fusion sarcomas. This supports the wider adoption of NGS panels including NTRK gene fusions.Table. Response to treatment"

Clinical • Fibrosarcoma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

LAROTRECTINIB (LARO) SAFETY AND EFFICACY IN PATIENTS (PTS) WITH TRK FUSION SARCOMAS AND PROLONGED RESPONSE (CTOS 2025) - No abstract available

Clinical • Oncology • Sarcoma • Solid Tumor

Pyrazolo[1,5-a]pyrimidine scaffold-based small molecules: From bench to FDA-approved TRK kinase inhibitors (Part 1). (PubMed, Eur J Med Chem) - "This review provides a critical analysis of small molecules bearing this heterocyclic motif, focusing on their chemical evolution, structure-activity relationship (SAR)- driven optimization, mechanistic insights into TRK inhibition, and the translational journey of these compounds from preclinical studies to FDA-approved drugs, such as Larotrectinib...This work aims to serve as a foundation for ongoing drug discovery efforts utilizing the pyrazolo[1,5-a]pyrimidine core in oncogenic kinase targeting. Collectively, this work underscores the significance of the pyrazolo[1,5-a]pyrimidine scaffold as a privileged chemotype and sets the stage for the rational development of next-generation TRK inhibitors with enhanced clinical utility."

FDA event • Journal • Review • Oncology

Extraskeletal osteosarcoma harboring ETV6::NTRK3 fusion treated successfully with larotrectinib: a case study. (PubMed, Commun Med (Lond)) - "This case represents the first reported instance of ESOS with an NTRK fusion. The rapid and sustained response to larotrectinib highlights the potential of precision medicine in managing rare and aggressive tumors, emphasizing the importance of molecular profiling to identify actionable targets."

Journal • Head and Neck Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Urothelial Cancer • ETV6 • NTRK • NTRK3

Larotrectinib for NTRK amplification in glioblastoma: Case report (WFNOS 2025) - "He underwent complete resection of the dominant lesion followed by concurrent temozolomide with radiation and 6 cycles of adjuvant temozolomide as well as tumor treating fields...Larotrectinib was discontinued and third line treatment with lomustine and bevacizumab was initiated...Our patient with glioblastoma harboring NTRK2 gene amplification did not have response to larotrectinib. Larotrectinib has demonstrated efficacy in gliomas with NRTK fusions but may not have efficacy in gliomas with NRTK amplifications."

Case report • Clinical • Brain Cancer • CNS Tumor • Esophageal Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor • MGMT • NTRK • NTRK1 • NTRK2

HTA Readiness for Tumor-Agnostic Therapies: Lessons From Analogues Across Major Markets (ISPOR-EU 2025) - "HTA outcomes and payer perceptions were analysed for pembrolizumab, entrectinib, larotrectinib and selpercatinib across 6 key global markets (Australia, Canada, England, France, Germany and Scotland) to determine commonalities and differences in payer reviews and constructive suggestions provided to the manufacturers by the payers. The evidence package for these tumor-agnostic drugs comprised of pooled results from multiple single arm trials. Tumor-agnostic therapies have faced payer scrutiny owing to evidence issues however, there were some signals that payers are willing to engage with manufacturers to provide patient access even without a robust evidence package. It is imperative for the manufacturers and the global market access teams to adopt a tumor-agnostic approach in evidence generation, such as pooled analysis of tumor types."

Pan tumor • Oncology

Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial) (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Biomarker • Trial completion date • Brain Cancer • CNS Tumor • Embryonal Tumor • Ependymoma • Ewing Sarcoma • Germ Cell Tumors • Glioma • Hematological Malignancies • Hepatoblastoma • High Grade Glioma • Langerhans Cell Histiocytosis • Lymphoma • Medulloblastoma • Nephrology • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Osteosarcoma • Pediatrics • Renal Cell Carcinoma • Rhabdoid Tumor • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Wilms Tumor