Trial reportCancer2014
Dual blockade of epidermal growth factor receptor and insulin-like growth factor receptor-1 signaling in metastatic pancreatic cancer: phase Ib and randomized phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus erlotinib (SWOG S0727).
Trial report in Cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 6 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
56 citing papers in PubMed, 6 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Chemotherapy and radiotherapy for advanced pancreatic cancer.The Cochrane database of systematic reviews · 2024Pooled it
- Chemotherapy and radiotherapy for advanced pancreatic cancer.The Cochrane database of systematic reviews · 2018Pooled it
- Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2017Pooled it
- Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.Nutrients · 2017Pooled it
- Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A systematic Review and Meta-Analysis.Clinical drug investigation · 2017Pooled it
- Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis.Drug design, development and therapy · 2016Pooled it
- Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma.Journal of hematology & oncology · 2018Trial
- Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.JAMA oncology · 2017Trial
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Pancreatic Cancer: Pathogenesis and Clinical Studies.MedComm · 2025Review
- The Effects of Juglone on Cell Proliferation and Insulin-Like Growth Factor I Receptor/Phosphoinositide 3-Kinase/p85 (IGF-IR/PI3K/p85) Signaling Pathway in Pancreatic Cancer.Journal of clinical practice and research · 2025Article
- Fibroblast PI3K/AKT signaling and extracellular matrix homeostasis: mechanisms, targets, and delivery challenges.Frontiers in cell and developmental biology · 2025Review
- Pancreatic Cancer: Beyond Brca Mutations.Journal of personalized medicine · 2022Review
- Preclinical Evaluation of a New Format ofPharmaceutics · 2022Article
- Molecular Characterization of KRAS Wild-type Tumors in Patients with Pancreatic Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Pharmacogenomics Testing in Phase I Oncology Clinical Trials: Constructive Criticism Is Warranted.Cancers · 2022Review
- Network controllability solutions for computational drug repurposing using genetic algorithms.Scientific reports · 2022Article
- The Intricate Crosstalk Between Insulin and Pancreatic Ductal Adenocarcinoma: A Review From Clinical to Molecular.Frontiers in cell and developmental biology · 2022Review
- Pancreatic Adenocarcinoma Therapeutics Targeting RTK and TGF Beta Receptor.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundTargeting a single pathway in pancreatic adenocarcinoma (PC) is unlikely to affect its natural history. We tested the hypothesis that simulataneous targeting of the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor-1 (IGF-1R) pathways would significantly improve progression-free survival (PFS) by abrogating reciprocal signaling that promote drug resistance
methodsThis was a phase Ib/II study testing cixutumumab, combined with erlotinib and gemcitabine (G) in patients with untreated metastatic PC. The control arm was erlotinib plus G. The primary end point was PFS. Eligibility included performance status 0/1 and normal fasting blood glucose. Polymorphisms in genes involved in G metabolism and in the EGFR pathway were also studied
resultsThe phase I results (n = 10) established the safety of cixutumumab 6 mg/kg/week intravenously, erlotinib 100 mg/day orally, and G 1000 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle. In the RP2 portion (116 eligible patients; median age, 63), the median PFS and overall survival (OS) were 3.6 and 7.0 months, respectively, on the cixutumumab arm, and 3.6 and 6.7 months, respecively, on the control arm. Major grades 3 and 4 toxicities with cixutumumab and control were elevation of transaminases, 12% and 6%, respectively; fatigue, 16% and 12%, respectively; gastrointestinal, 35% and 28%, respectively; neutropenia, 21% and 10%, respectively; and thrombocytopenia, 16% and 7%, respecively. Grade 3/4 hyperglycemia was seen in 16% of patients on cixutumumab. Grade 3 or 4 skin toxicity was similar in both arms of the study (< 5%). No significant differences in PFS by genotype were seen for any of the polymorphisms.
conclusionsAdding the IGF-1R inhibitor cixutumumab to erlotinib and G did not lead to longer PFS or OS in metastatic PC.
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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.