Table 2.
A list of the different GBM drugs, with a summary of the publically available preclinical and/or clinical results.
| Drug name | Preclinical/Clinical/results |
|---|---|
| Afatinib | Manageable safety profile but limited activity (Reardon et al., 2014b). |
| AFM21 | N.A. |
| Aldoxorubicin | Tumor growth delay observed in mice bearing U87-Luc tumors after injection of Aldoxorubicin (Marrero et al., 2014). |
| Altiratinib | Tumor growth delay observed in mice bearing GSC11 and GSC17 glioblastoma (Piao et al., 2016). |
| ANG1005 | Mice bearing U87 MG glioblastoma treated with ANG1005 display enhanced tumor growth delay compared with those treated with free paclitaxel (regina2008). |
| APG101 (Asunercept) | Phase II on 9 patients with recurrent glioblastoma: PFS at 6 months were 20.7% for RT + APG101 compared with 3.8% for RT alone. Improved survival warrants further studies for confiration (Wick et al., 2014). |
| AV0113 | N.A. |
| Avastin (bevacizumab) | Partial antitumor activity in mice with sarcoma tumors (Presta et al., 1997). Phases II and III: No improvement in survival when Avastin is used as first and second-line therapy, and both in association with cytotoxic treatment or alone (Lombardi et al., 2017). |
| BiCNU | N.A. |
| CBL0137 | IV injection of CBL0137 ± TMZ in mice bearing U87MG/A107 GBM Increases mouse maximum survival by 10–60 days. |
| Crenolanib | Glioma cell inhibition. |
| DCVax-L | Phase II suggests efficacy with 33% of patients reaching or exceeding median survival of 48 months and 27% reaching or exceeding median survival of 72 months. Two patients reached a survival of more than 10 years (Polyzoidis and Ashkan, 2014). Phase III on 331 patients on going. |
| Depatux-M; ABT-414 | Clinical trial on 66 patients leads to PFS at 6 months of 28.8%. |
| Enzastaurin | Phase III: 266 patients with recurrent glioblastoma treated. Enzastaurin well tolerated and better hematologic toxicity profile than lomustine but no superior efficacy compared with lomustine (Wick et al., 2010). |
| ERC-1671 | One patient receiving ERC-1671 survived for 10 months after the vaccine administration without any other adjuvant therapy and died of complications due his previous therapies (Bota et al., 2015). For 9 patients treated with ERC-1671, 6-month (26 weeks) survival for the nine Gliovac patients was 100 vs. 33% in control group (Schijns et al., 2015). |
| Gama Knife | Clinical results are too preliminary. Survival benefit still needs to be demonstrated in a phase III clinical study (Elaimy et al., 2013). |
| GDC-0084 | Mice bearing U87 MG glioblastoma injected with GDC-0084 exhibited tumor growth delay (Heffron et al., 2016). |
| Gliadel | 3 clinical trials with increased survival by 6–13 months. 3 clinical trials without increased survival, (Zhang et al., 2013). MA: 1998. |
| GMCI | 80% of mice bearing GL-261 tumors treated with PD-1 and GMCI cured (Speranza et al., 2018). |
| ICT-107 | Phase I: prolonged overall survival and PFS (preliminary data, Phupahnich et al., 2013). |
| IMA950 | Clinical Trial: 49 patients with GBM treated with IMA950. PFS was 74% at 6 months and 31% at 9 months. |
| Indoximod | Tumor growth delay observed in mice bearing GL-261 glioblastoma tumors injected with Indoximod (Hanihara et al., 2016). |
| KML001 | Clonogenic survival of GBM cells was significantly decreased by the combination of KML001 and TMZ or irradiation (Woo et al., 2014). |
| MEDI-575 | Phase II on 56 patients receiving MEDI-575 showed that MEDI-575 was well tolerated but had limited clinical activity (Phupahnich et al., 2013). |
| MgLITT (Neuroblate Visualase) | Treatment relatively well tolerated. Minimal BBB permeation (Carpentier et al., 2012). In 16 patients with GBM, Improved survival by 2 months (survival benefit warrants further study) (Schwarzmaier et al., 2006). |
| Mibefradil | Well tolerated and activity on some patients (Holdhoff et al., 2017). |
| Nanocell | First in man shows that nanocell was well tolerated in patients bearing glioblastoma (Whittle et al., 2015). |
| NOX-A12 | Mice bearing G12 GBM tumors injected with B-20 and NOX-12 led to an increase in maximum survival by 15 days. |
| Optune | Increase in time to disease progression from 13 to 26 weeks and of PFS6 from 15 to 50% and OS from 6 to 14.7 months (Saria and Kesari, 2016). |
| Panobinostat | Phase II on 15 patients, Panobinostat well tolerated, but no significant improvement in PFS6 compared with SOC (Lee et al., 2015). |
| Parvovirus | In a phase I study, parvovirus was well tolerated and immune response was observed (Geletneky et al., 2017). |
| Prophage | Phase II: Prophage + radiation and temozolomide lead to: (i) a 146% increase of PFS (17 months compared with 6.9 months for SOC), (ii) a 60% increase of OS (23.3 months compared with 14.6 months for SOC), (Chakraborty et al., 2016). |
| PSMA ADC | Phase II on 6 patients (trial NCT01856933), efficacy not observed (Elinzano et al., 2016). |
| Rindopepimut (CDX-110) | Phase II: demonstrating significantly increase by 10 months in PFS, minimal adverse effects (Babu and Adamson, 2012). Phase III (trial NCT01480479) did not confirm increases in PFS observed during phase II (Desaia et al., 2016; Gerstner, 2017; Weller et al., 2017). |
| SapC-DOPS | Tumor growth delay in mice bearing U87 (Wojton et al., 2013; Blanco et al., 2014, 2015). |
| Selenexor | Mice bearing patient derived GBM genograft model inhibit tumor growth delay following Selenexor injection (Green et al., 2014). |
| SurVaxM | Among 9 patients treated, 7 survived more than 12 months. Requires more clinical data to conclude about treatment efficacy (Fenstermaker et al., 2016). |
| Tandutinib | Phase II was closed due to a lack of efficacy (Batchelor et al., 2016). |
| TC-A2317 | GB neurosphere cells treated with alisertib for short periods undergo apoptosis (Van Brocklyn et al., 2014). |
| Temodar (Temozolomide) | Radiotherapy + Temozolomide: 2 months increase in overall survival, 15% increase in the percentage of patients alive after 2 years (Lee, 2017). Efficacy of TMZ limited due to MGMT that repairs DNA in tumor cells and reduces the effect of this alkylating agent and overexpression of EGFR. MA:2009. |
| Toca 511 + FC | High percentage of mice (40–100% depending on injected dose) bearing U87, Tu-2449 glioblastoma are alive 3–10 months following tumor cell implantation (Hiraoka et al., 2017). |
| Trebanaib AMG 386 | Phase II on 48 patients, treatment well tolerated but no improvement in survival (Reardon et al., 2018). |
| VAL-083 | Clinical trial (NCT02717962) ongoing. |
| VB-111 | Tumor growth delay in mice bearing U87-MG injected with VB-111 (Gruslova et al., 2015). |
M.A, Market Authorization; NA, Not Available.