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).

		OS					PFS
Variable	n	Events	Median [95% CI] T2E (months)	HR [95% CI]	p		Events	Median [95% CI] T2E (months)	HR [95% CI]	p
< 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.
Age					0.702					0.087
27-65	314	205	26.2 [22.1-29.8]				277	13.6 [11.1-13.8]
65-86	154	93	26.1 [23.0-33.9]	0.95 [0.74-1.22]			121	11.3 [9.5-14.3]	0.83 [0.67-1.03]
Sex					0.023					< 0.001
F	299	181	27.4 [24.2-32.9]				244	13.7 [12.4-16.4]
M	169	117	22.4 [19.6-27.7]	1.31 [1.04-1.66]			154	11.0 [8.4-12.0]	1.48 [1.21-1.81]
Race					0.514					0.875
Asian	404	260	26.1 [23.1-30.0]				349	13.6 [11.1-13.8]
Other/white	64	38	26.6 [21.1-33.9]	1.13 [0.78-1.65]			49	9.8 [6.8-13.7]	1.03 [0.74-1.42]
Smoking History					< 0.001					< 0.001
Never smoked	332	200	27.7 [24.8-31.7]				276	13.8 [13.6-15.7]
Ex or current smoker	136	98	20.2 [17.5-26.2]	1.53 [1.19-1.95]			122	8.9 [6.9-11.1]	1.56 [1.26-1.94]
Time since diagnosis					< 0.001					< 0.001
> 12 months	47	16	NA [34.3-NA]				32	19.4 [11.1-30.3]
< 12 months	421	282	24.2 [22.1-27.2]	2.65 [1.60-4.39]			366	12.1 [10.9-13.7]	2.00 [1.39-2.88]
Line of therapy					< 0.001					0.002
1st	442	289	24.8 [22.5-27.7]				381	12.5 [11.0-13.7]
2+	26	9	42.2 [32.9-NA]	0.38 [0.20-0.74]			17	19.4 [10.8-32.4]	0.51 [0.31-0.83]
ECOG PS					0.001					< 0.001
0	140	73	32.4 [27.2-NA]				108	13.7 [12.1-16.6]
1+	328	225	23.2 [20.5-26.8]	1.55 [1.18-2.04]			290	11.3 [9.8-13.7]	1.48 [1.18-1.86]
EGFR mutation type					< 0.001					< 0.001
DEL19	235	134	31.7 [28.1-35.3]				195	13.9 [13.7-16.5]
L858R	180	124	22.1 [19.6-25.8]	1.55 [1.21-1.98]			156	11.1 [9.6-13.7]	1.29 [1.05-1.60]
Other	41	30	17.3 [14.0-21.0]	2.01 [1.34-2.99]			35	6.9 [4.6-9.7]	1.82 [1.26-2.61]
T790M	11	9	20.8 [7.5-24.9]	3.11 [1.56-6.22]			11	2.8 [1.3-9.5]	3.84 [2.06-7.17]
Stage at screening					0.017					0.166
IIIB	34	16	42.2 [26.6-NA]				28	16.5 [9.7-22.1]
IV	434	282	24.8 [22.2-27.7]	1.76 [1.06-2.93]			370	12.7 [11.0-13.7]	1.30 [0.88-1.91]
No. of organs with metastases				1.56 [1.37-1.78]	< 0.001				1.36 [1.21-1.52]	< 0.001
BMI				0.96 [0.92-0.99]	0.009				0.95 [0.92-0.98]	< 0.001
Log SLD (mm)				1.74 [1.43-2.12]	< 0.001				1.81 [1.53-2.14]	< 0.001
Log ALP (U/L)				1.37 [1.15-1.63]	< 0.001				1.14 [0.98-1.34]	0.098
Log LDH (U/L)				1.92 [1.53-2.43]	< 0.001				1.52 [1.24-1.87]	< 0.001
Total protein (g/L)				0.99 [0.97-1.00]	0.101				0.99 [0.97-1.00]	0.135
Platelets > ULN					0.001					0.012
N	367	223	29.8 [25.4-32.1]				308	13.7 [11.1-13.9]
Y	101	75	20.0 [16.0-23.6]	1.58 [1.21-2.06]			90	10.8 [7.0-13.7]	1.37 [1.08-1.74]
Haemoglobin < LLN					< 0.001					< 0.001
N	367	220	29.3 [25.8-33.0]				305	13.7 [12.3-13.9]
Y	101	78	19.6 [16.6-22.1]	1.90 [1.46-2.49]			93	9.7 [6.9-11.0]	1.56 [1.23-1.99]
WBC > ULN					< 0.001					< 0.001
N	389	235	29.8 [26.1-32.1]				327	13.7 [12.7-14.4]
Y	79	63	15.1 [11.8-18.2]	2.42 [1.82-3.21]			71	6.9 [5.3-10.8]	1.90 [1.47-2.47]
Log NLR				1.73 [1.42-2.11]	< 0.001				1.47 [1.24-1.74]	< 0.001
Log LMR				0.54 [0.43-0.66]	< 0.001				0.66 [0.55-0.79]	< 0.001