Table 2 Molecular targeted therapy of LGG

Alkylating agent

Baumert et al. 2016

standard radiotherapy/primary temozolomide

Randomized phase III,

Open label

PFS

Median PFS (months)

IDHmt/codel 62

IDHmt/non-codel 48

IDHwt 20

There is no significant difference between radiotherapy alone and TMZ alone

Reijneveld et al. 2016

radiotherapy/temozolomide

Randomized phase III

Open label

PFS

Median PFS (months)

RT alone 46

TMZ alone 39

The effect of temozolomide or radiotherapy on HRQOL or global cognitive functioning

did not differ in LGG

Wahl et al. 2017

Adjuvant TMZ

Non-randomizes phase II

radiographic response rate

7 PR

Median PFS 3.8 years

Median OS 9.7 years

TMZ is beneficial as adjuvant therapy

Fisher et al. 2020

RT, TMZ, post-RT TMZ

Single arm

Phase II

OS

Median PFS 4.5 years

3-year OS rate 73.5%

5-year OS rate 60.9%

Combination of TMZ and RT is better than RT alone

Ras/Mek/Erk

Karajannis et al. 2014

Sorafenib

Non-randomized

Phase II

Open label

Sorafenib produced unexpected and unprecedented acceleration of tumor growth

Fangusaro et al. 2019

selumetinib

Non-randomized

Phase II

Open label

ORR

Stratum 1: 9 PR and 9 SD

Stratum 2: 10 PR and 15 SD

2-year PFS

Stratum 1: 70%

Stratum 2: 96%

Selumetinib is active against BRAF aberrations and NF-1 associated pLGG

Hargrave et al. 2019

Dabrafenib

Single arm phase I/IIa

Open label

ORR

1 CR and 13 PR

Median PFS 35.0 months

Dabrafenib is active

Perreault et al. 2019

Trametinib

Non-randomized

Phase II

Open label

ORR

(primary objective)

PI3K/AKT/mTOR

Ullrich et al. 2020

Everolimus

Non-randomized

Phase II

PFS at 48 weeks

1 CR and 3 PR(3D/volumetric analysis)

Everolimus is active against NF-1 associated patients

Wahl et al. 2017

Everolimus

Non-randomized

Phase II

PFS-6

PFS-6

Grade II 84%

Grade III/IV 55%

Median PFS (years)

Grade II 1.4

Grade III/IV 0.6

Median OS(years)

Grade II not reached

Grade III 2.9

Everolimus leads to disease stability