Trial reportBMC cancer2015
A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.
Trial report in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 36 papers.
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.
A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC
A Phase III, International, Randomised, Double Blind, Parallel-Group Study to Assess the Efficacy of Zactima™ Versus Tarceva® in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Failure of at Least One Prior Chemotherapy
A Phase III Study to Assess the Efficacy of ZD6474 (ZACTIMA™) Plus Best Supportive Care Versus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB-IV) Non-Small Cell Lung Cancer After Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)
A Phase III, Randomized, Double-blinded, Parallel Group, Multi-centre Study to Assess the Efficacy and Safety of ZD6474 (ZACTIMA™) in Combination With Pemetrexed (Alimta®) Versus Pemetrexed Alone in Patients With Locally-Advanced or Metastatic NSCLC
Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- An improved assay for detection of theranostic gene translocations and MET exon 14 skipping in thoracic oncology.Laboratory investigation; a journal of technical methods and pathology · 2021Trial
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- Immunohistochemistry in intrahepatic cholangiocarcinoma: histological subtyping and drug selection.Frontiers in oncology · 2025Review
- Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel.JTO clinical and research reports · 2024Article
- Review
- Review
- Expert consensus on the diagnosis and treatment of RET gene fusion non-small cell lung cancer in China.Thoracic cancer · 2023Article
- Amplification of Wild-TypeJCO precision oncology · 2023Article
- Review
- Treatment of Advanced Non-Small Cell Lung Cancer with RET Fusions: Reality and Hopes.International journal of molecular sciences · 2023Review
- Precision oncology with selective RET inhibitor selpercatinib inTherapeutic advances in medical oncology · 2023Review
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- Pralsetinib for the treatment of aAnnals of translational medicine · 2022Article
- Case Report: A novel intergenic MIR4299/MIR8070-RET fusion with RET amplification and clinical response to pralsetinib in a lung adenocarcinoma patient.Frontiers in oncology · 2022Article
- Non-small-cell lung cancer: how to manageDrugs in context · 2022Review
- [Advances in the Treatment of RET Fusion-positive Advanced Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- [Research Progress of Fusion Genes RET in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Therapeutic Advances in the Management of Patients with Advanced RET Fusion-Positive Non-Small Cell Lung Cancer.Current treatment options in oncology · 2021Review
- Novel Emerging Molecular Targets in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment.
methodsArchival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients.
resultsThe prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression.
conclusionsWe have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with efficacy in the RET rearrangement NSCLC subpopulation.
trial registrationRandomized Phase III clinical trials ( NCT00312377 , ZODIAC; NCT00418886 , ZEAL; NCT00364351 , ZEST; NCT00404924 , ZEPHYR).
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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.