Trial reportThe oncologist2018
Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors.
Trial report in The oncologist, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis.The Cochrane database of systematic reviews · 2021Pooled it
- Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.JAMA oncology · 2019Pooled it
- A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161.Investigational new drugs · 2022Trial
- Prioritization of chemical scaffolds using the TDR Targets database: An integrative workflow for Trypanosoma cruzi drug discovery.PLoS neglected tropical diseases · 2026Article
- Efficacy and Safety of Non-Surgical Treatments for Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Decoding Pancreatic Neuroendocrine Tumors: Molecular Profiles, Biomarkers, and Pathways to Personalized Therapy.International journal of molecular sciences · 2025Review
- Design of PI3K-mTOR Dual Inhibitors for Ovarian Cancer: Are we on the Right Track?Current medicinal chemistry · 2025Review
- Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.Cancers · 2024Review
- Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.Military Medical Research · 2024Review
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
- Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK).Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Review
- Molecular and functional imaging in cancer-targeted therapy: current applications and future directions.Signal transduction and targeted therapy · 2023Review
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- Integrated Molecular Characterization of Patient-Derived Models Reveals Therapeutic Strategies for Treating CIC-DUX4 Sarcoma.Cancer research · 2022Article
- Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.Nature reviews. Clinical oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 17 institutions in 6 countries.
Funding
Abstract
lessons learnedTreatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.The hypothesis of dual targeting of the phosphatidylinositol 3-kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents.
backgroundThis phase II study investigated whether targeting the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy.
methodsPatients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure.
resultsEnrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1-NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72-3.25). The most commonly reported all-grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%).
conclusionBEZ235 treatment in mTOR inhibitor-naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.
Indexed as
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What OpenQuestion holds
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.