Trial reportNeuro-oncology2015
Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma.
Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 8 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 8 pooled it
5.3field-weighted citation impact, top 4% of its field
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
122 citing papers in PubMed, 8 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- Predictive value of EGFR amplification and EGFRvIII mutation in EGFR-targeted therapy for recurrent glioblastoma: a systematic review.CNS oncology · 2026Pooled it
- Receptor tyrosine kinase targeted therapies in glioblastoma: a systematic review.Frontiers in medicine · 2026Pooled it
- Efficacy and safety of tyrosine kinase inhibitor combination therapy for glioblastoma: a meta-analysis with trial sequential analysis of randomized controlled trials.Frontiers in oncology · 2026Pooled it
- Targeted agents in patients with progressive glioblastoma-A systematic meta-analysis of randomized clinical trials.Cancer medicine · 2024Pooled it
- Efficacy and safety of pharmacotherapy for recurrent high-grade glioma: a systematic review and network meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Treatment options for progression or recurrence of glioblastoma: a network meta-analysis.The Cochrane database of systematic reviews · 2021Pooled it
- Optimal Therapies for Recurrent Glioblastoma: A Bayesian Network Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Anti-epidermal growth factor receptor therapy for glioblastoma in adults.The Cochrane database of systematic reviews · 2020Pooled it
- INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma.Neuro-oncology · 2020Trial
- Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase I cohorts of CheckMate 143.Neuro-oncology · 2018Trial
- Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification.Neuro-oncology · 2017Trial
- Continuous dose-intense temozolomide and cisplatin in recurrent glioblastoma patients.Medicine · 2017Trial
- Next-generation therapeutics for glioblastoma: Challenges and future directions.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- A novel quinazolinone insulin receptor inhibitor and its synergy with an EGFR inhibitor in glucose-driven glioblastoma.Molecular oncology · 2026Article
- Precision reirradiation in recurrent CNS tumors integrating biology techniques and multimodal care.Discover oncology · 2026Review
- A Genomically Tailored Multiagent Precision Medicine Clinical Trial for Adults with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- An alternative EGFR activation by patient-derived R252C mutation promotes cancer progression.Nature communications · 2026Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 13 institutions in 4 countries.
David A ReardonDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Louis B NaborsDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Warren P MasonDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
James R PerryDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
William ShapiroDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Petr KavanDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
David MathieuDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Surasak PhuphanichDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Agnieszka CsehDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Yali FuDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Julie CongDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
Sven WindDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
David D EisenstatDana-Farber Cancer Institute, Boston, Massachusetts (D.A.R.); University of Alabama, Birmingham, Alabama (L.B.N.); Princess Margaret Hospital, Toronto, Ontario, Canada (W.P.M.); Odette Cancer Centre, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (J.R.P.); Barrow Neurological Institute, Phoenix, Arizona (W.S.); Department of Medical Oncology, McGill University, Montréal, Quebec, Canada (P.K.); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada (D.M.); Johnnie Cochran Brain Tumor Center, Cedars-Sinai Medical Center, Los Angeles, California (S.P., A.C.); Boehringer Ingelheim R.C.V GmbH & Co KG, 1120 Vienna, Austria (A.C.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut (Y.F., J.C.); Boehringer Ingelheim Pharma GmbH & Co. K.G., 88400 Biberach, Germany (S.S.W.); CancerCare Manitoba, Winnipeg, Manitoba, Canada (D.D.E.).
BI 1200 36 Trial Group and the Canadian Brain Tumour Consortium
Barrow Neurological Institute · USBoehringer Ingelheim (Austria) · ATBoehringer Ingelheim (Germany) · DEBoehringer Ingelheim (United States) · USCancerCare Manitoba · CACedars-Sinai Medical Center · USCentre Hospitalier Universitaire de Sherbrooke · CADana-Farber Cancer Institute · USMcGill University · CAPrincess Margaret Cancer Centre · CAUniversity of Alabama at Birmingham · USUniversity of Alberta · CAUniversity of Toronto · CA
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM).
methodsPhase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m(2)/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m(2) for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression.
resultsRecommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants.
conclusionsAfatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients.
Indexed as
AdultAfatinibAgedAntineoplastic AgentsBrain NeoplasmsDacarbazineDrug Therapy, CombinationErb-b2 Receptor Tyrosine KinasesFemaleGlioblastomaHumansKaplan-Meier EstimateMaleMaximum Tolerated DoseMiddle AgedQuinazolinesAfatinibAntineoplastic AgentsDacarbazineErb-b2 Receptor Tyrosine KinasesQuinazolinesTemozolomideafatinibEGFRvIIIErbB familyglioblastomatemozolomide
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