Table 1.
Selected evidence for systemic treatment options in meningioma
| Drug | Drug class | Main inclusion criterion | Number of patients | Clinical phase | Outcome data | Ref |
|---|---|---|---|---|---|---|
| Hydroxyurea | Cytotoxic | Recurrent WHO grade 2–3 meningioma | n = 35 | Retrospective case series |
PFS-6: 3% Median PFS 2 months (95%CI 1.6–2.4) |
[12] |
| Recurrent WHO grade 1–2 meningioma | n = 12 | Prospective, phase not stated | Median time to progression (TTP): 13 months (range: 2–24) | [13] | ||
| Recurrent or unresectable WHO grade 1–3 meningioma | n = 20 | Prospective, phase not stated |
PFS-12: 93% PFS-24: 77% |
[14] | ||
| Recurrent WHO grade 1–3 meningioma | n = 4 | Retrospective case series | No aggregated data given | [15] | ||
| Recurrent WHO grade 2–3 meningioma | n = 13 | Phase 2 (unplanned post-hoc analysis) |
PFS-6: 8.8% Median PFS: 2.4 months (95%CI: 1.4–4.2) OS-6: 55.9% Median OS: 7.4 months (95%CI: 3.1–19.9) |
[21] | ||
| Irinotecan | Cytotoxic | Recurrent WHO grade 1 meningioma | n = 16 | Phase 2 |
PFS-6: 6% Median OS: 7 months |
[16] |
| Temozolomide | Cytotoxic | WHO grade 1–3 meningioma receiving radiotherapy | n = 11 | Retrospective case series | PFS-6: 91.7% | [17] |
| Recurrent WHO grade 1 meningioma | n = 16 | Phase 2 | Median TTP: 5 months (range: 2.5–5) | [18] | ||
| Vincristine, adriamycin, cyclophosphamide (VAC) | Cytotoxic | Treatment-naïve WHO grade 3 meningioma | n = 14 | Phase 2 |
Median TTP: 4.6 years (range: 2.2–7.1) Median OS: 5.3 years (range: 2.6–7.6) |
[19] |
| Trabectedin | Cytotoxic | Recurrent WHO grade 2–3 meningioma | n = 90 (trabectedin: n = 61; local standard of care: n = 29) | Phase 2 (local standard of care as control arm) |
Median PFS: 2.43 (trabectedin) vs. 4.17 months (local standard of care) PFS-6: 21.1% (trabectedin) vs. 29.1% (local standard of care) Median OS: 11.73 (trabectedin) vs. 10.61 months (local standard of care) |
[21] |
| Octreotide | Somatostatin analog | Recurrent WHO grade 1–3 meningioma or meningeal hemangiopericytoma | n = 12 | Phase 2 |
Median TTP: 17 weeks Median OS: 2.7 years (range: 22 days to 9.4 years) |
[23] |
| Recurrent WHO grade 2–3 meningioma | n = 9 | Phase 2 |
Median TTP: 4.23 months PFS-6: 44.4% |
[25] | ||
| Pasireotide | Somatostatin analog | Recurrent WHO grade 1–3 meningioma | n = 34 | Phase 2 |
WHO grade 1: - PFS-6: 50%, median PFS: 26 weeks (95%CI 12–43) WHO grade 2–3: - PFS-6: 17%, median PFS: 15 weeks (95%CI 8–20) |
[24] |
| Octreotide + everolimus | Somatostatin analog + mTOR inhibitor | Recurrent WHO grade 1–3 meningioma | n = 20 | Phase 2 |
PFS-6: 55% (95%CI: 31.1%-73.5%) OS-6: 90% (95%CI: 65.6%-97.4%) Decrease > 50% in tumor size in 78% of tumors |
[27] |
| 90Y-DOTATOC, 177Lu-DOTATOC | Radionucleid-somatostatin analog conjugate | Recurrent and unresectable WHO grade 1–3 meningioma | n = 34 | Phase 2 | Mean OS: 8.6 years | [26] |
| Sunitinib | Multi-tyrosine kinase inhibitor (VEGFR, PDGFR) | Recurrent WHO grade 2–3 meningioma | n = 36 | Phase 2 |
PFS-6: 42% Median PFS: 5.2 months (95%CI: 2.8–8.3) Median OS: 24.6 months (95%CI: 16.5–38.4) |
[31] |
| Vatalanib | Multi-tyrosine kinase inhibitor (VEGFR, PDGFR, c-kit) | Recurrent radiation- and surgery-refractory WHO grade 1–3 meningioma | n = 25 | Phase 2 |
WHO Grade 2: - PFS-6: 64.3% - Median PFS: 6.5 months - Median OS: 26.0 months WHO Grade 3: - PFS-6: 37.5%% - Median PFS: 3.6 months - Median OS: 23 months |
[33] |
| Bevacizumab | Monoclonal anti-VEGF antibody | WHO grade 2–3 meningioma | n = 15 | Retrospective case series |
PFS-6: 43.8% Median PFS: 26 weeks (95%CI: 10–29 weeks) |
[34] |
| Recurrent WHO grade 1–3 meningioma | n = 14 | Retrospective case series |
PFS-6: 86% Median PFS: 17.9 months (95%CI: 8.5 – not reached) Median OS: not reached |
[35] | ||
| Recurrent WHO grade 2–3 meningioma | n = 9 | Phase 2 (unplanned post-hoc analysis) |
PFS-6: 44.4% Median PFS: 6 months (95%CI: 2.1–18.6) OS-6: 88.9% Median OS: 13.5 months (95%CI: 5.4-not reached) |
[21] | ||
| Bevacizumab + everolimus | Monoclonal anti-VEGF antibody + mTOR inhibitor | Recurrent WHO grade 1–3 meningioma | n = 17 | Phase 2 |
PFS-6: 69% Median PFS: 22 months (95%CI: 4.5–26.8) Median OS: 23.8 months (95%CI: 9.0–33.1) |
[36] |
| Imatinib | Multi-tyrosine kinase inhibitor (PDGFR, c-kit, Bcr-abl) | Recurrent WHO grade 1–3 meningioma | n = 23 | Phase 2 |
PFS-6: 29.4% Median PFS: 2 months (range: 0.7–34) |
[39] |
| Imatinib + hydroxyurea | Multi-tyrosine kinase inhibitor (PDGFR, c-kit, Bcr-abl) + cytotoxic agent | Recurrent WHO grade 1–3 meningioma | n = 21 | Phase 2 |
PFS-6: 61.9% Median PFS: 7.0 months (95%CI: 2.8–9.2) Median OS: 66.0 months (95%CI: 20.7–66.0) |
[38] |
| Recurrent WHO grade 1–3 meningioma | n = 15 (imatinib + hydroxyurea: 7 patients; hydroxyurea alone: 8 pts) | Phase 2 |
Imatinib + hydroxyurea: - PFS-9: 0% - Median PFS: 4 months Hydroxyurea: - PFS-9: 75% - Median PFS: 19 months |
[40] | ||
| Erlotinib or gefitinib | Tyrosine kinase inhibitor (EGFR) | Recurrent WHO grade 1–3 meningioma | n = 25 (erlotinib: n = 9; gefitinib: n = 16) | Phase 2 (post-hoc analysis in pilot component of glioma trial) |
Whole cohort: - PFS-6: 28% - Median PFS: 10 weeks (95%CI: 8–20) - OS-6: 76% - Median S: 23 months (95%CI: 11-not reached) |
[41] |
| Vistusertib | mTOR inhibitor | Progressive or symptomatic meningiomas in patients with neurofibromatosis 2 | n = 18 | Phase 2 |
PFS-6: 88.9% Median PFS: not reached (95%CI: 24–not reached) |
[45] |
| AR-42 | Histone deacetylase inhibitor | NF2-associated vestibular schwannoma and meningioma and sporadic meningioma | n = 7 | Phase 1 (post-hoc analysis of phase 1 trial in advanced solid tumors) | No aggregated data, slowed tumor growth | [66] |
| IFN-α | Cytokine | Recurrent WHO grade 1 meningioma | n = 35 | Phase 2 |
PFS-6: 54% PFS-12: 31% Median TTP: 7 months (range: 2–24) Median OS: 8 months (range: 3–28) |
[67] |
| Recurrent WHO grade 2–3 meningioma | n = 35 | Retrospective case series |
PFS-6: 17% (95%CI: 7–31%) Median PFS: 12 weeks (95%CI: 8–20 weeks) |
[70] | ||
| Pembrolizumab | Monoclonal anti-PD-1 antibody | Recurrent and progressive WHO grade 2–3 meningioma | n = 25 | Phase 2 |
PFS-6: 48% (90%CI: 31–66%) Median PFS: 7.6 months (90%CI: 3.4–12.9) |
[84] |