Table 1. Intracranial efficacy of TKIs for EGFR- and ALK-positive NSCLC in recent select trials.

Study characteristics	AURA extension and AURA2 (13)	AURA3 (14)	OCEAN (15)	FLAURA (16)	ALEX (17)	CROWN (18)	Brigatinib trial (19)
Patient eligibility	T790M-positive, progressed following prior EGFR-TKI	T790M-positive, progressed following prior EGFR-TKI	T790M-positive, progressed following prior EGFR-TKI	Untreated EGFR mutation-positive advanced NSCLC	Untreated, ALK-positive NSCLC	ALK-positive NSCLC	ALK-positive NSCLC
BM eligibility	Stable, asymptomatic CNS metastases	Stable, asymptomatic CNS metastases	Radiation naïve BM, excludes BM requiring RT or resection	Asymptomatic, stable BM, or symptomatic, or unstable BM if stable for ≥2 weeks after therapy and steroids	Asymptomatic brain or leptomeningeal metastases, either treated or untreated	Asymptomatic CNS metastases, either treated or untreated, no prior radiation	Asymptomatic, untreated CNS metastases
Treatment	Osimertinib 80 mg daily	Osimertinib 80 mg daily	Osimertinib 80 mg daily	Osimertinib 80 mg daily (vs. gefitinib 250 mg or erlotinib 150 mg daily)	Alectinib 600 mg twice daily (vs. crizotinib 250 mg twice daily)	Lorlatinib 100 mg daily (vs. crizotinib 250 mg twice daily)	Brigatinib 180 mg daily (vs. crizotinib 250 mg twice daily)
Key results	iORR: 54%; median CNS DOR: not reached	iORR: 70%; median CNS DOR: 8.9 months	BMRR: 70%; iORR: 40.5%	Patients with measurable CNS lesions iORR: 91%; median CNS DOR: 15.2 months	Patients with measurable CNS lesions iORR: 81%	iORR: 82%; intracranial CR: 71%	Patients with measurable CNS lesions iORR: 78%

TKI, tyrosine kinase inhibitor; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase; NSCLC, non-small cell lung cancer; BM, brain metastases; CNS, central nervous system; iORR, intracranial objective response rate; DOR, duration of response; RT, radiation therapy; BMRR, brain metastases response rate; CR, complete response.