First-Line Osimertinib for Patients With EGFR Advanced NSCLC

Table 1. Baseline characteristics of 231 patients with EGFR-mutated advanced NSCLC receiving first line osimertinib
Characteristics	Value, n (%)
Age (years)
<65	70 (30.3)
65–74	88 (38.1)
≥75	73 (31.6)
Gender
Male	78 (33.8)
Female	153 (66.2)
ECOG PS
0/1	126 (54.5)
2/3	102 (44.2)
4	3 (1.3)
Histology
Adenocarcinoma	227 (98.3)
Adenosquamous	3 (1.3)
Squamous	1 (0.4)
Charlson Comorbidity Index, median (IQR)	0 (0–1)
Smoking status
Never smoker	136 (58.9)
Former smoker	83 (35.9)
Current smoker	12 (5.2)
EGFR mutation
19del	128 (55.4)
L858R	103 (44.6)
PD-L1 staining
<1%	89 (38.5)
1–49%	66 (28.6)
≥50%	68 (29.4)
Unknown	8 (3.5)
Brain metastases present	57 (24.7)
Initial stage at presentation
I	20 (8.7)
II	10 (4.3)
IIIA	9 (3.9)
IIIB	6 (2.6)
IIIC	2 (0.8)
IV	184 (79.7)
Advanced NSCLC at presentation	189 (81.8)

EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; IQR, interquartile range; PD-L1, programmed death ligand 1.

Table 2. Univariable and multivariable time dependent Cox regression analysis of progression free survival for 231 patients with EGFR-mutated advanced NSCLC treated with first-line osimertinib
Variables	Univariable		Multivariable
Variables	HR (95% CI)	P	HR (95% CI)	P
Age (≥75 vs. <75 years)	1.37 (0.93–2.00)	0.11	1.89 (1.25–2.78)	0.0021
Gender (male vs. female)	1.06 (0.72–1.56)	0.77	1.17 (0.82–1.69)	0.39
ECOG performance status
2/3 vs. 0/1	2.53 (1.72–3.72)	<0.001	2.45 (1.72–3.49)	<0.001
4 vs. 0/1	15.56 (4.72–51.31)	<0.001	22.27 (6.35–78.10)	<0.001
CCI (per 1 unit increase)	0.95 (0.80–1.13)	0.57	0.84 (0.71–1.00)	0.056
Smoking status
Former vs. never	1.44 (0.97–2.15)	0.070	1.01(0.69–1.48)	0.95
Current vs. never	4.77 (2.47–9.20)	<0.001	5.21 (2.90–9.36)	<0.001
Present with advanced NSCLC (yes vs. no)	1.23 (0.74–2.07)	0.42	0.85 (0.52–1.41)	0.53
Brain metastases at baseline (present vs. none)	1.37 (0.91–2.06)	0.13	1.29 (0.87–1.92)	0.21
EGFR mutation (L858R vs. 19del)	1.57 (1.08–2.27)	0.017	1.43 (1.00–2.06)	0.050
PD-L1 tumor proportion score
≥50% vs. <1%	1.74 (1.13–2.68)	0.012	1.59 (1.07–2.36)	0.023
1–49% vs. <1%	0.96 (0.59–1.55)	0.85	1.16 (0.75–1.80)	0.50
Unknown vs. <1%	0.99 (0.31–3.21)	0.99	0.99 (0.30–3.23)	0.99
Adverse event ≥ grade 2 (present vs. none)	1.20 (0.81–1.76)	0.36	0.79 (0.53–1.17)	0.24

CCI, Charlson Comorbidity Index; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; NSCLC, non-small cell lung cancer; PD-L1, programmed death ligand 1.

Table 3. Univariable and multivariable time dependent Cox regression analysis of overall survival for 231 patients with EGFR-mutated advanced NSCLC treated with first-line osimertinib
Variables	Univariable		Multivariable
Variables	HR (95% CI)	P	HR (95% CI)	P
Age (≥75 vs. <75 years)	1.45 (0.94–2.22)	0.087	1.42 (0.86–2.38)	0.16
Gender (male vs. female)	1.03 (0.67–1.58)	0.91	1.13 (0.71–1.81)	0.60
ECOG performance status
2/3 vs. 0/1	2.66 (1.72–4.12)	<0.001	2.46 (1.55–3.88)	<0.001
4 vs. 0/1	20.01 (5.94– 67.39)	<0.001	30.77 (8.51–111.34)	<0.001
CCI (per 1 unit increase)	1.03 (0.86–1.23)	0.75	0.91 (0.74–1.13)	0.39
Smoking status
Former vs. never	1.60 (1.04–2.48)	0.034	1.31 (0.81–2.12)	0.26
Current vs. never	3.23 (1.51–6.90)	0.002	2.91 (1.31–6.50)	0.0090
Present with advanced NSCLC (yes vs. no)	1.21 (0.67–2.17)	0.53	0.97 (0.50–1.89)	0.92
Brain metastases at baseline (present vs. none)	1.57 (1.00–2.45)	0.048	1.68 (1.04–2.71)	0.035
EGFR mutation (L858R vs. 19del)	1.61 (1.06–2.43)	0.025	1.26 (0.80–1.99)	0.32
PD-L1 tumor proportion score
≥50% vs. <1%	1.71 (1.06–2.76)	0.027	1.82 (1.10–2.99)	0.019
1–49% vs. <1%	0.92 (0.53–1.59)	0.76	1.14 (0.64–2.01)	0.66
Unknown vs. <1%	0.91 (0.22–3.82)	0.90	1.28 (0.30–5.48)	0.74
Adverse event ≥ grade 2 (present vs. none)	1.09 (0.73–1.63)	0.70	1.26 (0.78–2.02)	0.34

CCI, Charlson Comorbidity Index; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; NSCLC, non-small cell lung cancer; PD-L1, programmed death ligand 1.

Table 4. Adverse events ≥ grade 2 attributed to osimertinib during all follow-up
Adverse event	Grade 2, n (%)	Grade 3, n (%)	Grade 4, n (%)	Grade 5, n (%)
Any	85 (36.8)	35 (15.2)	2 (0.9)	1 (0.4)
Alopecia	1 (0.4)	0	0	0
Arthralgias	2 (0.9)	0	0	0
Cardiomyopathy	0	1 (0.4)	0	0
Diarrhea	22 (9.5)	6 (2.6)	0	0
Dermatitis	29 (12.6)	8 (3.5)	0	0
Fatigue	1 (0.4)	4 (1.7)	0	0
Hand and Foot Syndrome	1 (0.4)	0	0	0
Hepatitis	0	3 (1.3)	0	0
Increased creatinine	1 (0.4)	0	0	0
Mucositis	7 (3.0)	2 (0.9)	0	0
Nausea	4 (1.7)	1 (0.4)	0	0
Pancytopenia	1 (0.4)	1 (0.4)	0	0
Paronychia	13 (5.6)	3 (1.3)	0	0
Pericardial effusion	1 (0.4)	0	0	0
Peripheral edema	1 (0.4)	0	0	0
Pneumonitis	1 (0.4)	5 (2.2)	2 (0.9)	1 (0.4)
Thrombocytopenia	0	1 (0.4)	0	0

n, number of patients with adverse event; %, number of patients who developed adverse event/231

Table S1. Comparison of baseline characteristics amongst patients with ECOG performance status 0–1 (n=126) and 2–4 (n=105) at initiation of osimertinib
Characteristic	ECOG PS 0–1, n (%)	ECOG PS 2–4, n (%)	P
Age ≥75 years	38 (30.2)	35 (33.3)	0.71^‡
Gender			0.99†
Male	42 (33.3)	36 (34.3)
Female	84 (66.7)	69 (65.7)
EGFR mutation			0.48^†
del19	73 (57.9)	55 (52.4)
L858R	53 (42.1)	50(47.6)
PD-L1 expression			0.30^†
<50%/unknown	93 (73.8)	70 (66.7)
≥50%	33 (26.2)	35 (33.3)
Smoking status			0.11^†
Never	81 (64.3)	55 (52.4)
Former	41 (32.5)	42 (40.0)
Current	4 (3.2)	8 (7.6)
CCI, median	0	0	0.90^‡
Brain metastases (present)	22 (17.5)	35 (33.3)	0.008^†

†, P value for Chi-squared test; ‡, P value for Kruskal-Wallis rank sum test. Charlson Comorbidity Index, CCI; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; n, number of patients; PD- L1, programmed death ligand 1.

Authors and Disclosures

Suganija Lakkunarajah¹, Pauline T. Truong^1,2, Jeffrey N. Bone³, Curtis Hughesman⁴, Stephen Yip⁴, Deepu Alex⁴, Jason Hart^1,2, Philip Pollock¹, Sarah Egli¹, Melissa Clarkson¹, Mary Lesperance⁵ and Doran Ksienski^1,2

¹BC Cancer-Victoria, British Columbia, Canada; ²University of British Columbia, Victoria, British Columbia, Canada; ³Biostatistics, Clinical Research Support Unit, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada; ⁴BC Cancer-Vancouver, British Columbia, Canada; ⁵University of Victoria, Department of Mathematics and Statistics, Victoria, British Columbia, Canada

Correspondence to
Dr. Doran Ksienski, MD, FRCPC, MPH. BC Cancer-Victoria, 2410 Lee Avenue V8R 6V5, Victoria, British Columbia, Canada; University of British Columbia, Victoria, British Columbia, Canada. Email: dksienski@bccancer.bc.ca.

Contributions
(I) Conception and design: S Lakkunarajah, D Ksienski, M Lesperance, JN Bone, PT Truong; (II) Administrative support: S Lakkunarajah, D Ksienski, S Egli, M Clarkson; (III) Provision of study materials or patients: S Yip, C Hughesman, D Alex, S Lakkunarajah, D Ksienski; (IV) Collection and assembly of data: S Yip, C Hughesman, D Alex, S Lakkunarajah, D Ksienski, J Hart, P Pollock; (V) Data analysis and interpretation: S Yip, C Hughesman, D Alex, S Lakkunarajah, JN Bone, PT Truong, D Ksienski, M Lesperance; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Conflicts of Interest
All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-81/coif). PTT receives writing and royalty fees from UpToDate, Wolters Kluwer Health Publishing. SY has received consulting fees from Amgen, AstraZeneca, Bayer, Incyte, and Roche. DK has received a grant from the BC Cancer Foundation (Grant No. F22-05558) to support this manuscript and has received unrestricted educational grants from AstraZeneca and speaker honoraria from Merck and Bristol-Myers Squibb. The other authors have no conflicts of interest to declare.