Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2018
Selective RET kinase inhibition for patients with RET-altered cancers.
Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
235 citing papers in PubMed, 2 syntheses or guidelines pooled it, 426 citations in OpenAlex.
- The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis.Investigational new drugs · 2023Pooled it
- Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Guideline
- Long-term safety of selpercatinib for Rearranged during transfection (RET)-activated advanced solid tumors in LIBRETTO-001: differing patterns of adverse events over time.The oncologist · 2024Trial
- CNS Protective Effect of Selpercatinib in First-LineJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Intracranial Activity of Selpercatinib in Chinese Patients With AdvancedJCO precision oncology · 2023Trial
- Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial.The Lancet. Oncology · 2022Trial
- Intracranial Efficacy of Selpercatinib inClinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Efficacy of Selpercatinib inThe New England journal of medicine · 2020Trial
- Efficacy of Selpercatinib inThe New England journal of medicine · 2020Trial
- Identification of a RAS-activatingClinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- RET-driven osteoprotegerin expression links medullary thyroid cancer to osteoblastic bone metastases.Cell reports. Medicine · 2026Article
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- Circulatory compromise as a potential mechanism of fatal hepatic failure during long-term selpercatinib therapy: pharmacokinetic and clinical insights.Cancer chemotherapy and pharmacology · 2026Article
- Selpercatinib-induced Acalculous Cholecystitis in an Elderly Patient with RET Fusion-positive Non-small Cell Lung Cancer.Internal medicine (Tokyo, Japan) · 2026Article
- Combination of Selpercatinib and Trametinib Overcomes Resistance to RET Inhibitors in RET-Mutant Medullary Thyroid Carcinoma.JCO precision oncology · 2026Article
- RET signaling as a mediator of estrogen receptor positive breast cancer brain metastasis.Communications biology · 2026Article
- Safety and effectiveness of selpercatinib in patients with RET fusion-positive non-small cell lung cancer in real-world clinical practice: a postmarketing study in Japan.Japanese journal of clinical oncology · 2026Observational
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- Tyrosine Kinase Inhibitor Therapy in Metastatic Medullary Thyroid Carcinoma: Real-World Data from Turkish Oncology Group.Journal of clinical medicine · 2026Article
- Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
175 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
Abstract
Background: Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations. Patients and methods: Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly. Results: LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein -/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved. Conclusions: These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.