Table 2.

Post-hoc analysis of clinical trials on targeted agents in NSCLC: CNS relapse after first-line treatment.

Treatment Arm	Mutation Targeted	Brain Metastases	Time to CNS Relapse	Other Parameters of Secondary Prevention
Osimertinib [46]	EFGR	Absent or stable	N/A	Patients with new BM: 5%
Crizotinib [49]	ALK	Absent or pretreated + stable	N/A	Median time to intracranial progression: NR in both HR 0.69
Alectinib [50]	ALK	Absent or stable	HR: 0.16 12-month rate: 9.4%	N/A
Brigatinib [51]	ALK	Absent or treatment-naïve + stable	N/A	CNS as first site of progression: 9% No BM at baseline, 1%
Ceritinib [52]	ALK	Active	N/A	CNS as first site of progression: Arm 1 (prior RT + ALKi): 31% Arm 2 (no prior RT + prior ALKi): 60% Arm 3 (prior RT + no prior ALKi): 16.7% Arm 4 (no prior RT or ALKi): 50%
Lorlatinib [53]	ALK	Stable + treatment naïve or active + pretreated	N/A	No CNS progession at 12 months: 96% HR for intracranial progression of 0.07 CNS as first site of progression: 3% HR 0.06
Sotorasib [54]	KRASpG12C	Absent or stable	15.8 months HR of 0.52	N/A
Entrectinib [56]	ROS1	Stable	13.6 months	New CNS lesions: 4.5% (absent BM at baseline) CNS progression risk at 12 months: 39%
Selpercatinib [58]	RET	Stable or active with 14 days of stable symptoms, scans and steroid dosage	N/A	No BM at baseline: No CNS progression BM at baseline: 10% Cumulative incidence rates for CNS progression 6-months: 3% 12 months: 10% 18 months: 17% 24 months; 17% 36 months: 20%

CNS: central nervous system; ALKi: ALK inhibitor; RT: radiotherapy; N/A: not applicable.