Erlotinib for Japanese Patients with Activating EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Combined Analyses from Two Phase II Studies

Figures & data

Figure 1. Progression-free survival with first-line erlotinib in JO22903, JO25567 and combined populations.

PFS: Progression-free survival.

Figure 2. Univariate Cox regression analysis of progression-free survival.

ECOG PS: Eastern Cooperative Oncology Group performance status; HR: Hazard ratio; PFS: Progression-free survival.

Figure 3. Combined analysis of progression-free survival according to pleural/pericardial effusions at baseline.

HR: Hazard ratio; PFS: Progression-free survival.

Table 1. Baseline characteristics.

Characteristic	JO25567 (n = 77), n (%)	JO22903 (n = 100^†), n (%)	Combined population (n = 177), n (%)
Gender:
– Male:female	26 (34):51 (66)	33 (33):67 (67)	59 (33):118 (67)
Age (years):
– Median (range)	67 (36–84)	65 (36–86)	66 (36–86)
– ≥75 years	15 (20)	14 (14)	29 (16)
– <75 years	62 (81)	86 (86)	148 (84)
ECOG PS:
– 0	41 (53)	47 (47)	88 (50)
– 1	36 (47)	53 (53)	89 (50)
Stage:
– Recurrence	15 (20)	24 (24)	39 (22)
– Stage IIIB/IV	62 (81)	76 (76)	138 (78)
Smoking status:
– Nonsmoker	45 (58)	57 (57)	102 (58)
– Current/former smoker	32 (42)	43 (43)	75 (42)
EGFR mutation:
– L858R mutation	37 (48)	50 (50)	87 (49)
– Exon 19 deletion	40 (52)	50 (50)	90 (51)
Sum of baseline longest diameter of tumor (mm):
– ≥41	35 (45)	54 (54)	89 (50)
– <41	42 (55)	46 (46)	88 (50)
– ≥67	19 (25)	27 (27)	46 (26)
– <67–41	16 (21)	27 (27)	43 (24)
– <41–26	20 (26)	24 (24)	44 (25)
– <26	22 (29)	22 (22)	44 (25)
Number of affected organs:
– ≥3	45 (58)	81 (81)	126 (71)
– <3	32 (42)	19 (19)	51 (29)
PPE:
– Yes	36 (47)	33 (33)	69 (39)
– No	41 (53)	67 (67)	108 (61)
Brain metastases:
– Yes	NA	20 (20)	20 (11)
– No	77 (100)	80 (80)	157 (89)

^†Two patients with T790M mutation and one patient with a major protocol violation were excluded.

ECOG PS: Eastern Cooperative Oncology Group performance status; NA: Not applicable; PPE: Pleural/pericardial effusion.

Table 2. Multivariate Cox regression^† for progression-free survival.

Covariate	HR^‡	95% CI	p-value
Age:
– ≥75 vs <75 years	1.31	0.78–2.18	0.303
EGFR mutation:
– Exon 19 deletion vs L858R	0.74	0.49–1.12	0.148
Stage:
– Recurrence vs stage IIIB/IV	0.93	0.54–1.60	0.780
Gender:
– Female vs male	0.69	0.43–1.11	0.129
Smoking status:
– Nonsmoker vs current/former smoker	1.15	0.72–1.85	0.559
ECOG PS:
– O vs 1	0.67	0.45–0.99	0.046
Sum of baseline longest diameter of tumor (mm):
– <26 vs ≥67	0.56	0.30–1.07	0.078
– <41–26 vs ≥67	0.69	0.39–1.20	0.190
– <67–41 vs ≥67	1.06	0.64–1.77	0.820
Number of affected organs:
– ≥3 vs <3	1.15	0.71–1.86	0.578
PPE:
– No vs yes	0.38	0.25–0.58	<0.0001

^†All variables included in the analysis are described in the table.

^‡HR <1.0 means that PFS was better in the left group compared with the right group.

ECOG PS: Eastern Cooperative Oncology Group performance status; HR: Hazard ratio; PPE: Pleural/pericardial effusion.

Table 3. Sites of progression in patients who had disease progression following EGFR tyrosine kinase inhibitor treatment (n = 125).

Progression site	Patients (n)
Lung	101
Lymph nodes	31
Bone	20
Pleura	18
PPE	18
Liver	11
Brain^†	6
Adrenal grand	3
Kidney	2
Pericardial effusion	2
Peritoneum	1
Ovary	1
Ascites	1
Other	3

^†Two patients had carcinomatous meningitis at disease progression.

PPE: Pleural/pericardial effusion.

Table 4. Patient characteristics of six patients who had CNS progression.

Number	Age (years)	ECOG PS	EGFR mutation	Baseline CNS metastases	Erlotinib dose at PD (mg)	PFS (days)	Simultaneous progression site	Subsequent treatment after PD
1	50	1	19 del	No	100	106	None	Yes
2	55	1	19 del	Yes	150	335	Lung	Yes
3	55	0	L858R	No	150	168	Lung	Yes
4	73	1	L858R	Yes	150	80	Lung	Yes
5	60	0	L858R	No	150	188	None	None
6	54	0	L858R	Yes	100	377	Lung	Yes

del: deletion; ECOG PS: Eastern Cooperative Oncology Group performance status; PD: Progressive disease; PFS: Progression-free survival.

Table 5. Adverse events with an incidence of >20% or considered adverse events of special interest.

Adverse event	All grades, n (%)	Grade ≥3, n (%)
Rash^†	176 (99)	34 (19)
Diarrhea	141 (79)	2 (1)
Dry skin	125 (70)	5 (3)
Paronychia	118 (66)	4 (2)
Stomatitis	111 (62)	3 (2)
Pruritus	99 (56)	3 (2)
Hepatic dysfunction^†	93 (52)	28 (16)
Anorexia	61 (34)	4 (2)
Nasopharyngitis	53 (30)	0 (0)
Alopecia	43 (24)	0 (0)
Decreased weight	40 (23)	1 (1)
Nausea	38 (21)	1 (1)
Constipation	38 (21)	1 (1)
Dysgeusia	38 (21)	0 (0)
Interstitial lung disease^†	9 (5)	3 (2)^‡

^†Group term.

^‡Two of the three cases of grade ≥3 interstitial lung disease were grade 5.