2.

Cox multivariate analysis of OS from time of disease progression on crizotinib therapy and from time of initial crizotinib treatment in patients with documented progressive disease (N=261)

Characteristics	OS from crizotinib progression					OS from crizotinib initiation
	Univariable analysis		Multivariable analysis			Univariable analysis		Multivariable analysis
	HR (95% CI)	P	HR (95% CI)	P		HR (95% CI)	P	HR (95% CI)	P
OS, overall survival; ECOG PS, Eastern Cooperative Oncology Group performance status; PFS, progression-free survival; NA, not available; CBPD, crizotinib beyond progressive disease; ALK, anaplastic lymphoma kinase; HR, hazard ratio; 95% CI, 95% confidence interval.
ECOG PS
0−1vs. 2−3	0.385 (0.236−0.630)	<0.001	0.909 (0.525−1.574)	0.732		0.300 (0.184−0.490)	<0.001	0.635 (0.366−1.102)	0.107
Brain metastasis
Yes vs. No	0.881 (0.578−1.344)	0.557	0.867 (0.555−1.355)	0.530		0.917 (0.598−1.405)	0.690	0.870 (0.556−1.361)	0.543
No. of treatment lines before crizotinib
0 vs. ≥1	0.723 (0.515−1.040)	0.082	0.646 (0.439−0.951)	0.027		0.730 (0.512−1.040)	0.081	0.610 (0.413−0.901)	0.013
PFS with crizotinib
≥median vs. 　<median	0.478 (0.320−0.716)	<0.001	0.534 (0.353−0.809)	0.003		0.236 (0.156−0.359)	<0.001	0.188 (0.121−0.291)	<0.001
Progression pattern
Extracranial 　progress vs. 　intracranial 　progress	1.606 (1.031−2.502)	0.036	1.449 (0.883−2.379)	0.142		1.748 (1.120−2.730)	0.014	1.415 (0.869−2.303)	0.163
Comprehensive 　progress vs. 　intracranial 　progress	9.314 (5.543−15.649)	<0.001	7.322 (3.964−13.526)	<0.001		6.229 (3.760−10.321)	<0.001	5.408 (2.955−9.895)	<0.001
NA vs. 　intracranial 　progress	1.626 (0.678−3.900)	0.277	1.330 (0.519−3.411)	0.553		2.356 (0.980−5.665)	0.056	1.569 (0.613−4.019)	0.348
CBPD
Yes vs. No	0.467 (0.326−0.669)	<0.001	0.580 (0.372−0.905)	0.016		0.407 (0.284−0.585)	<0.001	0.556 (0.354−0.874)	0.011
Next-generation ALK inbibitors after progression on crizotinib
Yes vs. No	0.459 (0.307−0.686)	<0.001	0.310 (0.198−0.483)	<0.001		0.550 (0.368−0.824)	0.004	0.309 (0.195−0.489)	<0.001