S2

Univariate cox proportional hazard analysis of potential predictors of OS and PFS for patients treated with first-line afatinib (Lux-Lung 3 and 6).

OSPFS
Variablen EventsMedian [95% CI]
T2E (months) 		HR
[95% CI] 		p EventsMedian [95% CI]
T2E (months) 		HR
[95% CI] 		p
Age0.7020.087
27-6531420526.2
[22.1-29.8] 		27713.6
[11.1-13.8]
65-861549326.1
[23.0-33.9] 		0.95
[0.74-1.22] 		12111.3
[9.5-14.3] 		0.83
[0.67-1.03]
Sex0.023< 0.001
F29918127.4
[24.2-32.9] 		24413.7
[12.4-16.4]
M16911722.4
[19.6-27.7] 		1.31
[1.04-1.66] 		15411.0
[8.4-12.0] 		1.48
[1.21-1.81]
Race0.5140.875
Asian40426026.1
[23.1-30.0] 		34913.6
[11.1-13.8]
Other/white643826.6
[21.1-33.9] 		1.13
[0.78-1.65] 		499.8
[6.8-13.7] 		1.03
[0.74-1.42]
Smoking History< 0.001< 0.001
Never smoked33220027.7
[24.8-31.7] 		27613.8
[13.6-15.7]
Ex or current smoker1369820.2
[17.5-26.2] 		1.53
[1.19-1.95] 		1228.9
[6.9-11.1] 		1.56
[1.26-1.94]
Time since diagnosis< 0.001< 0.001
> 12 months4716NA
[34.3-NA] 		3219.4
[11.1-30.3]
< 12 months42128224.2
[22.1-27.2] 		2.65
[1.60-4.39] 		36612.1
[10.9-13.7] 		2.00
[1.39-2.88]
Line of therapy< 0.0010.002
1st44228924.8
[22.5-27.7] 		38112.5
[11.0-13.7]
2+26942.2
[32.9-NA] 		0.38
[0.20-0.74] 		1719.4
[10.8-32.4] 		0.51
[0.31-0.83]
ECOG PS0.001< 0.001
01407332.4
[27.2-NA] 		10813.7
[12.1-16.6]
1+32822523.2
[20.5-26.8] 		1.55
[1.18-2.04] 		29011.3
[9.8-13.7] 		1.48
[1.18-1.86]
EGFR mutation type< 0.001< 0.001
DEL1923513431.7
[28.1-35.3] 		19513.9
[13.7-16.5]
L858R18012422.1
[19.6-25.8] 		1.55
[1.21-1.98] 		15611.1
[9.6-13.7] 		1.29
[1.05-1.60]
Other413017.3
[14.0-21.0] 		2.01
[1.34-2.99] 		356.9
[4.6-9.7] 		1.82
[1.26-2.61]
T790M11920.8
[7.5-24.9] 		3.11
[1.56-6.22] 		112.8
[1.3-9.5] 		3.84
[2.06-7.17]
Stage at screening0.0170.166
IIIB341642.2
[26.6-NA] 		2816.5
[9.7-22.1]
IV43428224.8
[22.2-27.7] 		1.76
[1.06-2.93] 		37012.7
[11.0-13.7] 		1.30
[0.88-1.91]
No. of organs with metastases1.56
[1.37-1.78] 		< 0.0011.36
[1.21-1.52] 		< 0.001
BMI0.96
[0.92-0.99] 		0.0090.95
[0.92-0.98] 		< 0.001
Log SLD (mm)1.74
[1.43-2.12] 		< 0.0011.81
[1.53-2.14] 		< 0.001
Log ALP (U/L)1.37
[1.15-1.63] 		< 0.0011.14
[0.98-1.34] 		0.098
Log LDH (U/L)1.92
[1.53-2.43] 		< 0.0011.52
[1.24-1.87] 		< 0.001
Total protein (g/L)0.99
[0.97-1.00] 		0.1010.99
[0.97-1.00] 		0.135
Platelets > ULN0.0010.012
N36722329.8
[25.4-32.1] 		30813.7
[11.1-13.9]
Y1017520.0
[16.0-23.6] 		1.58
[1.21-2.06] 		9010.8
[7.0-13.7] 		1.37
[1.08-1.74]
Haemoglobin < LLN< 0.001< 0.001
N36722029.3
[25.8-33.0] 		30513.7
[12.3-13.9]
Y1017819.6
[16.6-22.1] 		1.90
[1.46-2.49] 		939.7
[6.9-11.0] 		1.56
[1.23-1.99]
WBC > ULN< 0.001< 0.001
N38923529.8
[26.1-32.1] 		32713.7
[12.7-14.4]
Y796315.1
[11.8-18.2] 		2.42
[1.82-3.21] 		716.9
[5.3-10.8] 		1.90
[1.47-2.47]
Log NLR1.73
[1.42-2.11] 		< 0.0011.47
[1.24-1.74] 		< 0.001
Log LMR0.54
[0.43-0.66] 		< 0.0010.66
[0.55-0.79] 		< 0.001

< LLN, below the lower limit of normal; > ULN, above the upper limit of normal; ALP, alkaline phosphatase; BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; LMR, lymphocyte to monocyte ratio; SLD, sum of longest tumour diameters; NLR, neutrophil to lymphocyte ratio; WBC, white blood cells.