Randomized Phase II Trial of Erlotinib Versus Temozolomide or Carmustine in Recurrent Glioblastoma: EORTC Brain Tumor Group Study 26034

Bent, Martin J. van den; Brandes, Alba A.; Rampling, Roy; Kouwenhoven, Mathilde C.M.; Kros, Johan M.; Carpentier, Antoine F.; Clément, Paul M.; Frénay, M.; Campone, Mario; Baurain, Jean‐François; Armand, Jean-Paul; Taphoorn, Martin J.B.; Tosoni, Alicia; Kletzl, Heidemarie; Klughammer, Barbara; Lacombe, Denis; Gorlia, Thierry

doi:10.1200/jco.2008.17.5984

Cited by 486 publications

(271 citation statements)

References 19 publications

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“…This would be in agreement with the other authors that have postulated that tumors harboring certain point mutations, as well as the vIII deletion, would be more responsive to dacomitinib (21). In fact, the presence of EGFRvIII, in a wild-type PTEN context, had been associated with GBM response to erlotinib (15), although this could not be confirmed in subsequent trials (24). Retrospective analysis of the two current phase II clinical trials would help to solve these discrepancies.…”

Section: Discussionsupporting

confidence: 59%

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

Zahonero

Aguilera

Ramírez-Castillejo

et al. 2015

Molecular Cancer Therapeutics

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Glioblastomas (GBM) are devastating tumors in which there has been little clinical improvement in the last decades. New molecularly directed therapies are under development. EGFR is one of the most promising targets, as this receptor is mutated and/or overexpressed in nearly half of the GBMs. However, the results obtained with first-generation tyrosine-kinase inhibitors have been disappointing with no clear predictive markers of tumor response. Here, we have tested the antitumoral efficacy of a second-generation inhibitor, dacomitinib (PF299804, Pfizer), that binds in an irreversible way to the receptor. Our results confirm that dacomitinib has an effect on cell viability, self-renewal, and proliferation in EGFR-amplified AE EGFRvIII GBM cells. Moreover, systemic administration of dacomitinib strongly impaired the in vivo tumor growth rate of these EGFR-amplified cell lines, with a decrease in the expression of stem cell-related markers. However, continuous administration of the compound was required to maintain the antitumor effect. The data presented here confirm that dacomitinib clearly affects receptor signaling in vivo and that its strong antitumoral effect is independent of the presence of mutant receptor isoforms although it could be affected by the PTEN status (as it is less effective in a PTEN-deleted GBM line). Dacomitinib is being tested in second line for EGFR-amplified GBMs. We hope that our results could help to select retrospectively molecular determinants of this response and to implement future trials with dacomitinib (alone or in combination with other inhibitors) in newly diagnosed GBMs. Mol Cancer Ther; 14(7); 1548-58. Ó2015 AACR.

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Section: Discussionsupporting

confidence: 59%

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

Zahonero

Aguilera

Ramírez-Castillejo

et al. 2015

Molecular Cancer Therapeutics

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“…Nitrosoureas [52][53][54][55][56] and 1 trial with carmustine where data for patients treated with carmustine (n=29) were not separately reported but summarized in a common "control" arm with 27 patients receiving TMZ [57]. All but 3 trials were conducted at the first recurrence after TMZ-based standard radiochemotherapy.…”

Section: Nitrosourea Monotherapy and Combination Regimensmentioning

confidence: 99%

“…All but 3 trials were conducted at the first recurrence after TMZ-based standard radiochemotherapy. One study was done in chemotherapy-naïve-patients [47], one study did not disclose previous chemotherapy except exclusion of nitrosourea, bevacizumab or investigational agents [53], one study reported previous chemotherapy in about 60% of the patients without details [57]. PFS-6 ranged between 17.5% and 61.5% and median OS between 6.0 and 11.1 months for monotherapy of nitrosourea agents.…”

Section: Nitrosourea Monotherapy and Combination Regimensmentioning

confidence: 99%

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Therapeutic options in recurrent glioblastoma—An update

Seystahl

Wick

Weller

2016

Critical Reviews in Oncology/Hematology

177

134

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“…A subset of glioblastomas exhibit overexpression of egfr and EGFR gene amplification 111 , and several trials have investigated the egfr tyrosine kinase inhibitors erlotinib, gefitinib, and lapatinib. However, a phase ii trial that compared erlotinib with active controls (temozolomide or carmustine) reported a 6-month pfs of only 11.4% as compared with 24% for controls 112 . Other trials have reported little or no benefit for erlotinib used as a single agent or in combination with carboplatin or sirolimus, a mammalian target of rapamycin (mtor) inhibitor [113][114][115] .…”

Section: 64mentioning

confidence: 99%

Canadian Recommendations for the Treatment of Recurrent or Progressive Glioblastoma Multiforme

Easaw¹,

Mason²,

Perry³

et al. 2011

Current Oncology

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Recommendation 1: Multidisciplinary Approach: To optimize treatment outcomes, the management of patients with recurrent glioblastoma should be individualized and should involve a multidisciplinary team approach, including neurosurgery, neuropathology, radiation oncology, neuro-oncology, and allied health professions. Recommendation 2: Imaging: The standard imaging modality for assessment of recurrent glioblastoma is Gd-enhanced magnetic resonance imaging (MRI). Tumour recurrence should be assessed according to the criteria set out by the Response Assessment in Neuro-Oncology Working Group. The optimal timing and frequency of MRI after chemoradiation and adjunctive therapy have not been established. Recommendation 3: Pseudo-progression: Progression observed by MRI after chemoradiation can be pseudo-progression. Accordingly, treated patients should not be classified as having progressive disease by Gd-enhancing MRI within the first 12 weeks after the end of radiotherapy unless new enhancement is observed outside the radiotherapy field or viable tumour is confirmed by pathology at the time of a required re-operation. Adjuvant temozolomide should be continued and follow-up imaging obtained. Recommendation 4: Repeat Surgery: Surgery can play a role in providing symptom relief and confirming tumour recurrence, pseudo-progression, or radiation necrosis. However, before surgical intervention, it is essential to clearly define treatment goals and the expected impact on prognosis and the patient’s quality of life. In the absence of level 1 evidence, the decision to re-operate should be made according to individual circumstances, in consultation with the multidisciplinary team and the patient. Recommendation 5: Re-irradiation: Re-irradiation is seldom recommended, but can be considered in carefully selected cases of recurrent glioblastoma. Recommendation 6: Systemic Therapy: Clinical trials, when available, should be offered to all eligible patients. In the absence of a trial, systemic therapy, including temozolomide rechallenge or antiangiogenic therapy, may be considered. Combination therapy is still experimental; optimal drug combinations and sequencing have not been established.

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Randomized Phase II Trial of Erlotinib Versus Temozolomide or Carmustine in Recurrent Glioblastoma: EORTC Brain Tumor Group Study 26034

Abstract: Erlotinib has insufficient single-agent activity in unselected GBM. No clear biomarker associated with improved outcome to erlotinib was identified.

Cited by 486 publications

References 19 publications

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

Preclinical Test of Dacomitinib, an Irreversible EGFR Inhibitor, Confirms Its Effectiveness for Glioblastoma

Therapeutic options in recurrent glioblastoma—An update

Canadian Recommendations for the Treatment of Recurrent or Progressive Glioblastoma Multiforme

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