Table 3.
Therapies targeting autocrine and paracrine pathways inducing proneural–mesenchymal transition.
| Target | Agent | Clinical trial (reference) |
|---|---|---|
| EGFR | Afatinib | Phase II in unselected recurrent GBM: manageable safety profile but limited single-agent activity (ClinicalTrials.gov NCT01743950)126 |
| Depatuxizumab mafodotin | Phase III in newly-diagnosed GBM: no OS benefit and no new important safety risks (ClinicalTrials.gov NCT02573324)127 | |
| Phase II in recurrent EGFR-amplified GBM: had no impact on HRQoL and NDFS (ClinicalTrial.gov NCT02343406)128 | ||
| Pulse high-dose lapatinib | Phase II in newly-diagnosed GBM: tolerable and safe regimen, but higher rates of lymphopenia should be noted (ClinicalTrial.gov NCT01591577)129 | |
| Anti-EGFR-immunoliposomes | Phase II in EGFR-amplified GBM: showed active but warrant further clinical evaluation (ClinicalTrial.gov NCT03603379)130 | |
| Rindopepimut | Phase III in newly diagnosed, EGFRvIII-expressing GBM: did not increase survival (ClinicalTrials.gov NCT01480479)132 | |
| TGF-β | Galunisertib | Phase II of with Galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in newly diagnosed malignant GBM: no differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms (ClinicalTrials.gov NCT01220271)133 |
| Trabedersen | Phase II in high-grade glioma: 10 μM is the optimal dose (ClinicalTrials.gov NCT00431561)134 | |
| VEGF | Bevacizumab | Phase II of bevacizumab with either irinotecan in recurrent GBM: showed therapeutic benefit (ClinicalTrials.gov NCT00433381)135 |
| Phase II of bevacizumab + dose-dense temozolomide in recurrent GBM: showed confirming activity (ClinicalTrials.gov NCT00433381)135 | ||
| Phase II of bevacizumab + vorinosta in recurrent GBM: did not yield improvement in PFS, OS or clinical benefit (ClinicalTrials.gov NCT01266031)137 | ||
| Phase II of bevacizumab + trebananib in recurrent GBM: showed minimal activity (ClinicalTrials.gov NCT01609790)138 | ||
| Phase III of bevacizumab + lomustine in progressive GBM: did not confer a survival advantage over treatment with lomustine alone (ClinicalTrials.gov NCT01290939)139 | ||
| Ponatinib | Phase II in bevacizumab-resistant GBM: limited efficacy (ClinicalTrials.gov NCT02478164)136 | |
| Aflibercept | Phase II in recurrent malignant GBM: moderate toxicity and minimal evidence of single-agent activity (ClinicalTrials.gov NCT00369590)140 | |
| FGFR | Nintedanib | Phase II in recurrent GBM regardless of prior bevacizumab therapy: no active (ClinicalTrials.gov NCT01380782)141 |
| Dovitinib | Phase II in recurrent GBM: was not efficacious in prolonging the PFS (ClinicalTrials.gov NCT01753713)142 | |
| PDGFR | Nintedanib | Phase II in recurrent GBM: well tolerated and clinically non-relevant antitumor activity (ClinicalTrials.gov NCT01380782)141 Phase II in recurrent GBM: not active (ClinicalTrial.gov NCT01251484)143 |
| Dasatinib | Phase II in recurrent GBM: ineffective (ClinicalTrials.gov NCT00423735)144 |