Table 1.
Targeted therapies in glioblastoma, currently under clinical trial or completed.
| Medication | Target | Population | Phase | Comedication | Overall Survival (OS) | Progression-Free Survival (PFS) |
|---|---|---|---|---|---|---|
| Vemurafenib [58] | V600E BRAF V600D BRAF V600R BRAF |
Patients with BRAF-V600-mutant glioma in any point of treatment | Phase II | n.a. | 11.9 months (95% CI, 8.3 to 40.1 months) for malignant diffuse glioma | 5.3 months (95% CI, 1.8 to 12.9 months) for malignant diffuse glioma |
| Dabrafenib [59,60] | V600E BRAF
V600D BRAF V600R BRAF V600K BRAF |
Patients with recurrent or progressive BRAF V600E–mutant HGG and LGG | Phase II | trametinib | 17.6 months (95% CI, 9.5 to 45.2 months) for HGG | 3.8 months (95% CI, 1.8 to 9.2 months) for HGG |
| Patients with BRAF-V600-mutant solid tumors (including GBM), lymphomas, or multiple myeloma | Phase II | trametinib | 28.6 months for all types of cancers | 11.4 months (90% CI, 8.4 to 16.3 months) for all types of cancers | ||
| Trametinib [59,60] | MEK1/2 | |||||
| Cobimetinib [61] | MEK1 | Paediatric and young adult patients with relapsed or refractory solid tumors (including HGG) | Phase I/II | n.a. | not reached | 14.8 months (95 % CI, 3.6 to 14.8) for all types of cancers |
| Paxalisib [62] | PI3K/mTOR | Patients with newly-diagnosed GBM with unmethylated MGMT promoter status following surgical resection and initial chemoradiation with temozolomide | Phase II | n.a. | 15.7 months | 8.4 months |
| Everolimus [63,64,65] | mTOR | Patients with newly diagnosed GBM | Phase II | everolimus + radiotherapy + temozolomide vs. radiotherapy + temozolomide | 16.5 months (95% CI, 12.5 to 18.7 months) vs. 21.2 months (95% CI, 16.6 to 29.9 months) | 8.2 months (95% CI, 6.5 to 10.6 months) vs. 10.2 months (95% CI, 7.5 to 13.8 months) |
| everolimus + radiotherapy + temozolomide | 15.8 months (95% CI, 13.0 to 20.3 months) | 6.4 months (95% CI, 5.4 to 9.0 months) | ||||
| Patients with newly diagnosed GBM, previously not treated | Phase II | radiotherapy + temozolomide + bevacizumab followed by the combination of bevacizumab + everolimus | 13.9 months (95% CI, 12.4 to NA months) | 11.3 months (95% CI, 9.3 to 13.1 months) | ||
| Nintedanib [66] | VEGFR1-R3 and FGFR1–3 | First or second recurrence of GBM in patients previously treated with bevacizumab vs. not treated with bevacizumab | Phase II | n.a. | 2.6 months (95% CI, 1.0 to 6.9 moths) vs. 6.9 months (95% CI, 3.7 to 8.1 months) | 0.9 months (95% CI, 0.7 to 0.9 months) vs. 0.9 months (95% CI, 0.9 to 2.8 months) |
| Pemigatinib [67] | FGFR1–3 | Patients with recurrent GBM or other primary CNS tumors with an activating FGFR1-3 mutation or fusion/rearrangement | Phase II | n.a. | Ongoing | Ongoing |
| Aflibercept [68] | VEGF-A/B | Patients with recurrent malignant or anaplastic gliomas that did not respond to temozolomide | Phase II | n.a. | 9.8 months | 3.0 months (95% CI, 2.0 to 4.0 months) |
| Bevacizumab [69,70,71] |
VEGF-A | Patients with GBM with progression after chemoradiation | Phase III | bevacizumab + lomustine vs. lomustine monotherapy | 9.1 months (95% CI, 8.1 to 10.1 months) vs. 8.6 months (95% CI, 7.6 to 10.4 months) |
4.2 months (95% CI, 3.7 to 4.3 months) vs. 1.5 months (95% CI, 1.5 to 2.5 months) |
| Patients with first or second relapse and GBM progression | Phase II | bevacizumab monotherapy vs. bevacizumab + irinotecan | 9.2 months (95% CI, 8.2 to 10.7 months) vs. 8.7 months (95% CI, 7.8 to 10.9 months) | 4.2 months (95% CI, 2.9 to 5.8 months) vs. 5.6 months (95% CI, 4.4 to 6.2 months) | ||
| Patients with recurrent GBM after chemoradiation | Phase II | n.a. | 7.8 months (95% CI, 5.3 to 13.5 months) | 4.0 months (95% CI, 3.0 to 6.5 months) |
||
| Pazopanib [72] | VEGFR1-R3 | Patients with recurrent GBM | Phase II | n.a. | 8.6 months (95% CI, 6 to 11.8 months) | 3.0 months (95% CI, 2.0 to 3.5 months) |
| Sorafenib [73,74,75] | VEGFR2-R3 | Patients with newly diagnosed GBM, previously not treated | Phase II | radiotherapy + temozolomide followed by the combination of temozolomide + sorafenib | 12.0 months (95%CI, 7.2 to 16.0 months) | 6.0 months (95% CI, 3.7 to 7.0 months) |
| Patients with recurrent GBM | Phase II | temozolomide | 10.4 months (95% CI, 6.0 to 13.8 months), | 1.6 months (95% CI, 1.0 to 2.9 months) | ||
| Patients with progressive/recurrent GBM | Phase II | erlotinib | 5.7 months (95% CI, 4.5 to 7.9 months) | 2.5 months (95% CI, 1.8 to 3.7 months) | ||
| Sunitinib [76] | VEGFR1-R2 | Patients with recurrent GBM | Phase II/III | sunitinib vs. lomustine | Ongoing | Ongoing |
| Lenvatinib [77] | VEGFR1-R3 | Patients with previously treated select solid tumors (including GBM) | Phase II | pembrolizumab | Ongoing | Ongoing |
| Apatinib [78] | VEGFR2 | Patients with recurrent GBM | Phase II | temozolomide | 9.0 months (95% CI, 8.2 to 12.2 months) | 6.0 months (95% CI, 5.3 to 7.8 months) |
| Regorafenib [79] | VEGFR1-3 | Patients with relapsed GBM | Phase II | regorafenib monotherapy vs. lomustine monotherapy | 7.4 months (95% CI, 5.8 to 12.0 months) vs. 5.6 months (95% CI, 4.7 to 7.3 months) | 2.0 months (95% CI, 1.9 to 3.6 months) vs. 1.9 months (95% CI, 1.8 to 2.1 months) |
| Vemurafenib [58] | V600E BRAF V600D BRAF V600R BRAF |
Patients with BRAF-V600-mutant glioma in any point of treatment | Phase II | n.a. | 11.9 months (95% CI, 8.3 to 40.1 months) for malignant diffuse glioma | 5.3 months (95% CI, 1.8 to 12.9 months) for malignant diffuse glioma |
| Dabrafenib [59,60] | V600E BRAF
V600D BRAF V600R BRAF V600K BRAF |
Patients with recurrent or progressive BRAF V600E–mutant HGG and LGG | Phase II | trametinib | 17.6 months (95% CI, 9.5 to 45.2 months) for HGG | 3.8 months (95% CI, 1.8 to 9.2 months)) for HGG |
| Patients with BRAF-V600-mutant solid tumors (including GBM), lymphomas, or multiple myeloma | Phase II | trametinib | 28.6 months for all types of cancers | 11.4 months (90% CI, 8.4 to 16.3 months) for all types of cancers | ||
| Trametinib [59,60] | MEK1/2 | JAK WYŻEJ | ||||
| Cobimetinib [61] | MEK1 | Pediatric and young adult patients with relapsed or refractory solid tumors (including HGG) | Phase I/II | n.a. | not reached | 14.8 months (95% CI, 3.6 to 14.8) for all types of cancers |
| Paxalisib [62] | PI3K/mTOR | Patients with newly diagnosed GBM with unmethylated MGMT promoter status following surgical resection and initial chemoradiation with temozolomide | Phase II | n.a. | 15.7 months | 8.4 months |
| Everolimus [63,64,65] | mTOR | Patients with newly diagnosed GBM | Phase II | everolimus + radiotherapy + temozolomide vs. radiotherapy + temozolomide | 16.5 months (95% CI, 12.5 to 18.7 months) vs. 21.2 months (95% CI, 16.6 to 29.9 months) | 8.2 months (95% CI, 6.5 to 10.6 months) vs. 10.2 months (95% CI, 7.5 to 13.8 months) |
| everolimus + radiotherapy + temozolomide | 15.8 months (95% CI, 13.0 to 20.3 months) | 6.4 months (95% CI, 5.4 to 9.0 months) | ||||
| Patients with newly diagnosed GBM, previously not treated | Phase II | radiotherapy + temozolomide + bevacizumab followed by the combination of bevacizumab + everolimus | 13.9 months (95% CI, 12.4 to NA months) | 11.3 months (95% CI, 9.3 to 13.1 months) | ||
| Nintedanib [66] | VEGFR1-R3 and FGFR1–3 | First or second recurrence of GBM in patients previously treated with bevacizumab vs. not treated with bevacizumab | Phase II | n.a. | 2.6 months (95% CI, 1.0 to 6.9 moths) vs. 6.9 months (95% CI, 3.7 to 8.1 months) | 0.9 months (95% CI, 0.7 to 0.9 months) vs. 0.9 months (95% CI, 0.9 to 2.8 months) |
| Pemigatinib [67] | FGFR1–3 | Patients with recurrent GBM or other primary CNS tumors with an activating FGFR1-3 mutation or fusion/rearrangement | Phase II | n.a. | Ongoing | Ongoing |
| Aflibercept [68] | VEGF-A/B | Patients with recurrent malignant or anaplastic gliomas that did not respond to temozolomide | Phase II | n.a. | 9.8 months | 3.0 months (95% CI, 2.0 to 4.0 months) |
| Bevacizumab [69,70,71] | VEGF-A | Patients with GBM with progression after chemoradiation | Phase III | bevacizumab + lomustine vs. lomustine monotherapy | 9.1 months (95% CI, 8.1 to 10.1 months) vs. 8.6 months (95% CI, 7.6 to 10.4 months) |
4.2 months (95% CI, 3.7 to 4.3 months) vs. 1.5 months (95% CI, 1.5 to 2.5 months) |
| Patients with first or second relapse and GBM progression | Phase II | bevacizumab monotherapy vs. bevacizumab + irinotecan | 9.2 months (95% CI, 8.2 to 10.7 months) vs. 8.7 months (95% CI, 7.8 to 10.9 months) | 4.2 months (95% CI, 2.9 to 5.8 months) vs. 5.6 months (95% CI, 4.4 to 6.2 months) | ||
| Patients with recurrent GBM after chemoradiation | Phase II | n.a. | 7.8 months (95% CI, 5.3 to 13.5 months) | 4.0 months (95% CI, 3.0 to 6.5 months) |
||
| Pazopanib [72] | VEGFR1-R3 | Patients with recurrent GBM | Phase II | n.a. | 8.6 months (95% CI, 6 to 11.8 months) | 3.0 months (95% CI, 2.0 to 3.5 months) |
| Sorafenib [73,74,75] | VEGFR2-R3 | Patients with newly diagnosed GBM, previously not treated | Phase II | radiotherapy + temozolomide followed by the combination of temozolomide + sorafenib | 12.0 months (95%CI, 7.2 to 16.0 months) | 6.0 months (95% CI, 3.7 to 7.0 months) |
| Patients with recurrent GBM | Phase II | temozolomide | 10.4 months (95% CI, 6.0 to 13.8 months), | 1.6 months (95% CI, 1.0 to 2.9 months) | ||
| Patients with progressive/recurrent GBM | Phase II | erlotinib | 5.7 months (95% CI, 4.5 to 7.9 months) | 2.5 months (95% CI, 1.8 to 3.7 months) | ||
| Sunitinib [76] | VEGFR1-R2 | Patients with recurrent GBM | Phase II/III | sunitinib vs. lomustine | Ongoing | Ongoing |
| Lenvatinib [77] | VEGFR1-R3 | Patients with previously treated select solid tumors (including GBM) | Phase II | pembrolizumab | Ongoing | Ongoing |
| Apatinib [78] | VEGFR2 | Patients with recurrent GBM | Phase II | temozolomide | 9.0 months (95% CI, 8.2 to 12.2 months) | 6.0 months (95% CI, 5.3 to 7.8 months) |
| Regorafenib [79] | VEGFR1-3 | Patients with relapsed GBM | Phase II | regorafenib monotherapy vs. lomustine monotherapy | 7.4 months (95% CI, 5.8 to 12.0 months) vs. 5.6 months (95% CI, 4.7 to 7.3 months) | 2.0 months (95% CI, 1.9 to 3.6 months) vs. 1.9 months (95% CI, 1.8 to 2.1 months) |