Trial reportThe Lancet. Oncology2016
Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial.
Trial report in The Lancet. Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 251 papers, 3 of them syntheses that pooled it.
What it found
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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.
A Phase II Study of Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity
"Phase II Study to Evaluate the Activity and Safety of Cabozantinib in Pretreated, Advanced RET-rearranged Non-small Cell Lung Cancer Patients: CRETA Trial"
Who cites it
251 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Pooled it
- 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
- Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With AdvancedJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Trial
- Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial.Signal transduction and targeted therapy · 2025Trial
- Efficacy of Selpercatinib inThe New England journal of medicine · 2020Trial
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- 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
- Research progress of small molecule targeted drugs for non-small cell lung cancer.Frontiers in oncology · 2026Review
- An evolving landscape: predictive and therapeutic biomarkers in advanced non-small cell lung cancer.Frontiers in oncology · 2026Review
- Advances in Targeted Therapy for Non-Small-Cell Lung Cancer: Current Progress and Future Directions.International journal of molecular sciences · 2025Review
- Real-world FAERS safety analysis of Pralsetinib.Scientific reports · 2025Article
- Targeting mesenchymal-epithelial transition factor signaling in cancer: from genetic alterations to clinical advances and future prospects.Molecular biology reports · 2025Review
- A Phase II Study of Cabozantinib in Patients WithJTO clinical and research reports · 2025Article
- Advances in molecular pathology and therapy of non-small cell lung cancer.Signal transduction and targeted therapy · 2025Review
- Responsiveness of different MET tumour alterations to type I and type II MET inhibitors.Clinical and translational medicine · 2025Article
- Clinical characterization and therapeutic targeting of fusion genes in oncology.Future oncology (London, England) · 2025Review
- The Research Progress of Neurotrophic Tyrosine Receptor KinaseIranian journal of public health · 2025Review
- Next-Generation Sequencing in Oncology-A Guiding Compass for Targeted Therapy and Emerging Applications.International journal of molecular sciences · 2025Review
- Review
191 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
backgroundRET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with lung cancers. To assess the activity of cabozantinib in patients with RET-rearranged lung cancers, we did a prospective phase 2 trial in this molecular subgroup.
methodsWe enrolled patients in this open-label, Simon two-stage, single-centre, phase 2, single-arm trial in the USA if they met the following criteria: metastatic or unresectable lung cancer harbouring a RET rearrangement, Karnofsky performance status higher than 70, and measurable disease. Patients were given 60 mg of cabozantinib orally per day. The primary objective was to determine the overall response (Response Criteria Evaluation in Solid Tumors version 1.1) in assessable patients; those who received at least one dose of cabozantinib, and had been given CT imaging at baseline and at least one protocol-specified follow-up timepoint. We did safety analyses in the modified intention-to-treat population who received at least one dose of cabozantinib. The accrual of patients with RET-rearranged lung cancer to this protocol has been completed but the trial is still ongoing because several patients remain on active treatment. This study was registered with ClinicalTrials.gov, number NCT01639508.
findingsBetween July 13, 2012, and April 30, 2016, 26 patients with RET-rearranged lung adenocarcinomas were enrolled and given cabozantinib; 25 patients were assessable for a response. KIF5B-RET was the predominant fusion type identified in 16 (62%) patients. The study met its primary endpoint, with confirmed partial responses seen in seven of 25 response-assessable patients (overall response 28%, 95% CI 12-49). Of the 26 patients given cabozantinib, the most common grade 3 treatment-related adverse events were lipase elevation in four (15%) patients, increased alanine aminotransferase in two (8%) patients, increased aspartate aminotransferase in two (8%) patients, decreased platelet count in two (8%) patients, and hypophosphataemia in two (8%) patients. No drug-related deaths were recorded but 16 (62%) patients died during the course of follow-up. 19 (73%) patients required dose reductions due to drug-related adverse events.
interpretationThe reported activity of cabozantinib in patients with RET-rearranged lung cancers defines RET rearrangements as actionable drivers in patients with lung cancers. An improved understanding of tumour biology and novel therapeutic approaches will be needed to improve outcomes with RET-directed targeted treatment.
fundingExelixis, National Institutes of Health and National Cancer Institute Cancer Center Support Grant P30 CA008748.
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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.