A Prospective Observational Study of Osimertinib for Chemo-Naive Elderly Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer

Figures & data

Table 1 Patient Characteristics

	n=43 (%)
Age (years), median, range	79 (75–90)
Gender
Female/Male	24 (56)/19 (44)
Performance status
0–1/2	33 (77)/10 (23)
EGFR genotype
Del 19/L858R	24 (56)/19 (44)
Histology
Adenocarcinoma	43 (100)
Stage
IV/Recurrence	30 (70)/13 (30)
Smoking status
Current smoker	18 (42)
Never or former light smoker	25 (58)
Brain metastasis
Negative/Positive	34 (79)/9 (21)

Table 2 Response to Osimertinib Therapy

	n=43
Complete response	0
Partial response	26
Stable disease	14
Progressive disease	3
Response rate	60.5%
95% CI	44.9–76.0

Table 3 Univariate and Multivariate Analyses for Factors That May Influence Progression-Free Survival

Variable	Univariate Analysis		Multivariate Analysis
	Hazard Ratio (95% CI)	P-value	Hazard Ratio (95% CI)	P-value
Sex
Female	1 (Ref.)	0.68
Male	1.22 (0.47–3.19)
Performance status
0–1	1 (Ref.)	0.08	1 (Ref.)	0.021
2	2.62 (0.89–7.69)
			3.94 (1.23–12.7)
Smoking status
Never	1 (Ref.)	0.19	Excluded
Smoker	1.91 (0.73–4.98)
Stage
Stage IV	1 (Ref.)	0.018	1 (Ref.)	0.006
Recurrence	0.31 (0.12–0.82)		0.24 (0.08–0.66)
Brain metastasis
Negative	1 (Ref.)	0.19	Excluded
Positive	2.00 (0.70–5.71)
Type of EGFR mutation
L858R	1 (Ref.)
Del. 19	0.91 (0.35–2.40)	0.86

Abbreviations: CI, confidence interval; Del 19, exon 19 deletion; L858R, exon 21 point mutation.

Table 4 Univariate and Multivariate Analyses for Factors That May Influence Time to Treatment Failure

Variable	Univariate Analysis		Multivariate Analysis
	Hazard Ratio (95% CI)	P-value	Hazard Ratio (95% CI)	P-value
Sex
Female	1 (Ref.)	0.65
Male	1.21 (0.53–2.75)
Performance status
0–1	1 (Ref.)	0.047	1 (Ref.)	0.015
			3.35 (1.27–8.86)
2	2.53 (1.01–6.33)
Smoking status
Never	1 (Ref.)	0.31
Smoker	1.53 (0.67–3.49)
Stage
Stage IV	1 (Ref.)	0.023	1 (Ref.)	0.008
			0.31 (0.13–0.74)
Recurrence	0.38 (0.17–0.88)
Brain metastasis
Negative	1 (Ref.)	0.11	Excluded
Positive	2.05 (0.84–4.99)
Type of EGFR mutation
L858R	1 (Ref.)
Del. 19	0.91 (0.40–2.08)	0.87

Figure 1 Kaplan–Meier curves showing (A) progression free survival (PFS) and (B) time to treatment failure (TTF) to osimertinib therapy.

Figure 2 Kaplan–Meier curves showing (A) PFS and (B) TTF in patients receiving osimertinib therapy according to their Eastern Cooperative Oncology Group performance status score.

Table 5 Toxicities

Adverse Event	Any Grade (%)	Grade 1 (%)	Grade 2 (%)	Grade 3 (%)	Grade 4 (%)
Rash acneiform	18 (42)	13 (30)	5 (12)	0	0
Diarrhea	14 (33)	14 (33)	0	0	0
Paronychia	12 (27)	9 (21)	3 (6)	0
Oral mucositis	7 (16)	7 (16)	0	0	0
Anorexia	6 (13)	5 (11)	1 (2)	0	0
Dry skin	3 (6)	3 (6)	0	0
Fatigue	3 (6)	2 (4)	1 (2)	0
Nausea	2 (4)	2 (4)	0	0
Dysgeusia	2 (4)	2 (4)	0
Neutropenia	7 (16)	4 (10)	2 (4)	1 (2)	0
Leukopenia	6 (13)	5 (11)	1 (2)	0	0
Anemia	6 (13)	2 (4)	1 (2)	3 (7)	0
Thrombocytopenia	5 (11)	3 (7)	2 (4)	0	0
Creatinine increased	5 (11)	3 (7)	1 (2)	1 (2)	0
AST/ALT increased	4 (10)	4 (10)	0	0	0
QTc prolongation	2 (4)	0	2 (4)	0	0
Interstitial lung disease	8 (18)	4 (10)	3 (6)	1 (2)	0

Figure 3 Durations of treatment with osimertinib before disease progression or cessation owing to adverse events in individual patients.

Table 6 Clinical Studies on Patients ≥75 Years of Age Who Were Treated with EGFR-TKIs

	Drug	No of Pts.	Study Design	EGFR Mutation Type (Del. 19/L858R)	Age (Years)	Median Age (Range)	Response Rate (%)	Median PFS (Months)
Maemondo (11)	GEF	31	Prospective	Not reported	≥ 75	80 (75–89)	74.0	12.3
Takeishi (15)	GEF	55	Retrospective	31/24	≥ 75	81 (75–94)	72.7	13.8
Kuwako (16)	GEF	62	Retrospective	24/38	≥ 75	80 (75–89)	61.3	13.2
Inoue (18)	ERL	32	Prospective	12/20	≥ 75	80 (85–87)	56.3	15.5
Minegishi (20)	AFA	40	Prospective	23/15	≥ 75	78 (75–91)	75.7	14.2
Present report	OSIM	43	Prospective	24/19	≥ 75	79 (75–90)	60.5	22.1

Abbreviations: Pts, patients; PFS, progression-free survival; GEF, gefitinib; ERL, erlotinib; AFA, afatinib; OSIM, Osimertinib.