Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches

Table 4

Summary of the proportion of initial and recurrent of IDH-wildtype and IDH-mutant glioblastoma patient tumours that had SNVs that could be assigned as potentially clinically actionable.

Gene	IDH-wildtype				IDH-mutant				Frequency in GBM (Sahm et al.)	Targeted agent (clinical trial)
	Initial tumour		Recurrent tumour		Initial tumour		Recurrent tumour
	N	%	N	%	N	%	N	%	%
PIK3CA	2/38	5	0/7	0	0/3	0	0/1	0	6.3	mTOR inhibitor; everolimus (NCT02449538); BKM120/everolimus (NCT01470209)
PIK3R1	2/38	5	0/7	0	0/3	0	0/1	0		mTOR inhibitor
EGFR	6/38	16	1/7	14	0/3	0	0/1	0	34	ABBV-221 (NCT02365662); naratinib (NCT01953926); AZD9291 (NCT02465060); EGFR-targeting antibodies, vaccines, TK inhibitors, osimertinib, poziotinib
PDGFRA	2/38	5	0/7	0	0/3	0	0/1	0	11	Dasatinib; nilotinib/Pazopanib (NCT02029001); MGCD516 (NCT02219711)
BRAF	1/38	3	0/7	0	0/3	0	0/1	0		Vemurafenib; MEK inhibitor
PTEN	11/38	29	1/7	14	0/3	0	0/1	0	32	INC280/BKM120 (NCT01870726); everolimus (NCT02449538); erlotinib, everolimus or dasatinib (NCT02233049); GSK2636771 (NCT01458067); BMN673 (NCT02286687); BKM120/everolimus (NCT01470209)
BRCA1	7/38	18	1/7	14	0/3	0	0/1	0		Olaparib
BRCA2	7/38	18	1/7	14	1/3	33	0/1	0		Olaparib
PTCH1	1/38	3	0/7	0	0/3	0	0/1	0		SMO inhibitor, sonidegib and vismodegib
SMO	3/38	8	0/7	0	0/3	0	0/1	0		SMO inhibitor, sonidegib and vismodegib
ATR	3/38	8	0/7	0	0/3	0	0/1	0		ATR inhibitor (BAY1895344)
MSH6	4/38	11	0/7	0	1/3	33	0/1	0	4.3	MK-3475 (NCT01876511)
TP53	7/38	18	0/7	0	3/3	100	0/1	0
CDKN2A	3/38	8	0/7	0	0/3	0	0/1	0
RB1	1/38	3	0/7	0	0/3	0	0/1	0
ATM	6/38	16	1/7	14	0/3	0	0/1	0

For particular genetic alterations, the proportion of glioblastomas (n = 47) with alterations in those genes, as recorded by Sahm et al. [30], is also provided. Also summarised are available and new therapeutic agents currently on trial in clinical studies targeting molecular aberrations.