Table 4.

Surrogate endpoints for OS (tumor size variables)

Population	Variable	HR (95% CI)a	P-valueb
Patients with adenocarcinoma histology NSCLC
All	SLD of target lesions at 2 months after randomization (cm)	1.005 (1.003–1.006)	<0.0001
	ETS (any tumor increase, without new metastases vs new metastases)	0.574 (0.422–0.781)	0.0004
	ETS (minor tumor shrinkage vs new metastases)	0.711 (0.542–0.934)	0.0143
	PFS duration (months)	0.994 (0.992–0.995)	<0.0001
	PFS flag (PFS censoring vs PFS event)	0.570 (0.445–0.730)	<0.0001
TSFLT, 9 months	SLD of target lesions at 2 months after randomization (cm)	1.004 (1.002–1.006)	0.0002
	PFS duration (months)	0.994 (0.992–0.995)	<0.0001
	PFS flag (PFS censoring vs PFS event)	0.566 (0.416–0.770)	0.0003
PD-FLT	SLD of target lesions at baseline (cm)	1.007 (1.003–1.010)	0.0004
	PFS duration (months)	0.992 (0.989–0.995)	<0.0001
	Time to return to baseline SLD of target lesions (months)	1.001 (1.000–1.002)	0.0021
Patients with squamous cell histology NSCLC
	SLD of target lesions at 2 months after randomization (cm)	1.006 (1.004–1.007)	<0.0001
	TTG (months)	1.080 (1.015–1.148)	0.0143
	PFS duration (months)	0.993 (0.992–0.995)	<0.0001
	PFS flag (PFS censoring vs PFS event)	0.474 (0.351–0.639)	<0.0001

Notes:

^aPlease note that the HRs are not treatment effects. An HR of 1.005 as in line 1 means that an uptake in SLD at 2 months of 10 cm increases the risk of death by 5%.

^bScore test.

Abbreviations: ETS, early tumor shrinkage; HR, hazard ratio; NSCLC, non-small-cell lung cancer; OS, overall survival; PD-FLT, progressive disease as the best response to first-line therapy; PFS, progression-free survival; SLD, sum of longest diameter; TSFLT, time from start of first-line therapy to randomization; TTG, time to tumor growth.