3.1. All patients
3.1.1 Patient characteristics
Between September 2002 and June 2019, a total of 314 patients with ED-SCLC were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69 (range, 43–89) years; 82% of the patients were males, 70% had a performance status (PS) of 0 or 1, 97% were past or current smoker, 98% had stage IV disease, and 34% of the patients had brain metastasis (Table 1).
Table 1
Patient characteristics during first-line treatment
|
Number of patients
(n = 314)
|
Age (years)
|
|
Median
|
69
|
Range
|
43–89
|
≥ 75, n (%)
|
74 (24)
|
Gender, n (%)
|
|
Male
|
258 (82)
|
Female
|
56 (18)
|
PS at first-line treatment, n (%)
|
|
0–1
|
221 (70)
|
2–4
|
93 (30)
|
Stage at diagnosis, n (%)
|
|
stage IV
|
308 (98)
|
Other
|
6 (2)
|
Smoking Status, n (%)
|
|
Current or Former
|
306 (97)
|
Never
|
6 (2)
|
Unknown
|
2 (1)
|
Metastatic site, n (%)
|
|
Lung
|
53 (17)
|
Pleural effusion or dissemination
|
108 (34)
|
Brain
|
108 (34)
|
Liver
|
85 (27)
|
Bone
|
90 (29)
|
Adrenal gland
|
57 (18)
|
Regimen of first-line treatment, n (%)
|
|
Cisplatin plus Etoposide
|
39 (12)
|
Cisplatin plus Irinotecan
|
87 (28)
|
Carboplatin plus Etoposide
|
155 (49)
|
Other
|
33 (11)
|
Subsequent chemotherapy, n (%)
|
|
Yes
|
222 (71)
|
No
|
92 (29)
|
Relapse pattern of patients treated with subsequent systemic therapy, n (%)
|
|
Sensitive relapse
|
157 (50)
|
Refractory relapse
|
65 (21)
|
Abbreviations: PS: performance status |
Carboplatin plus etoposide was the most commonly used drug and was administered to 155 patients (49%) while cisplatin plus irinotecan and cisplatin plus etoposide were administered in 28% and 12% of the patients, respectively. Subsequent chemotherapy was administered in 222 patients (71%) and amrubicin was most frequently administered drug.
3.1.2. Efficacy
The overall response rate (ORR) of first-line treatment was 80% in all patients with ED-SCLC (Table 2).
Table 2
Best response to first-line treatment
|
Number of patients (N = 314)
|
Early group (N = 127)
|
Late group (N = 187)
|
Best response, n (%)
|
|
|
|
CR
|
6 (2)
|
3 (2)
|
3 (2)
|
PR
|
245 (78)
|
96 (76)
|
149 (80)
|
SD
|
26 (8)
|
8 (6)
|
18 (10)
|
PD
|
16 (5)
|
7 (5)
|
9 (5)
|
NE
|
21 (7)
|
13 (11)
|
8 (4)
|
Response rate (%)
|
80
|
78
|
81
|
p-value
|
|
0.470
|
Abbreviations: CR: complete response, PR: partial response, SD: stable disease, PD: progressive disease, NE: not evaluable |
The median follow-up time for OS was 7.4 years (95% CI: 4.7–8.9 years), and event was observed in 280 patients (89%). MST and mPFS was 12.1 months (95% CI: 10.8–13.1 months) and 4.9 months (95% CI: 4.6–5.2 months), respectively (Figure 1). One-year, two-year, three-year, and five-year survival rates were 49%, 14%, 6%, and 2%, respectively. MST in patients with PS of 0-1, who seemed to be included in the IMpower133 trial, was 13.4 months and five-year survival rate was only 3%.
3.2. Early group and late group
3.2.1. Patient characteristics
In total, 127 and 187 patients were grouped into the early and late groups, respectively. There was no significant difference in gender, PS at first-line treatment, and smoking status between the two groups (Table 3).
Table 3
Patient characteristics in the early and late groups
|
Early Group
(n = 127)
|
Late Group
(n = 187)
|
p-value
|
Age (years)
|
|
|
|
Median
|
67
|
70
|
|
Range
|
43–86
|
51–89
|
0.017
|
≥ 75, n (%)
|
27 (21)
|
47 (25)
|
0.4273
|
Gender, n (%)
|
|
|
|
Male
|
105 (83)
|
153 (82)
|
|
Female
|
22 (17)
|
34 (18)
|
0.845
|
PS at first-line treatment, n (%)
|
|
|
|
0–1
|
90 (71)
|
131 (70)
|
|
2–4
|
37 (29)
|
56 (30)
|
0.877
|
Stage at diagnosis, n (%)
|
|
|
|
stage IV
|
122 (96)
|
186 (99)
|
|
Other
|
5 (4)
|
1 (1)
|
0.031
|
Smoking Status, n (%)
|
|
|
|
Current or Former
|
123 (97)
|
183 (97)
|
|
Never
|
3 (2)
|
3 (2)
|
|
Unknown
|
1 (1)
|
1 (1)
|
0.856
|
Metastatic site, n (%)
|
|
|
|
Lung
|
32 (25)
|
21 (11)
|
0.001
|
Pleural effusion or dissemination
|
46 (36)
|
62 (33)
|
0.575
|
Brain
|
44 (35)
|
64 (34)
|
0.939
|
Liver
|
31 (24)
|
54 (29)
|
0.382
|
Bone
|
37 (29)
|
53 (28)
|
0.879
|
Adrenal gland
|
22 (17)
|
35 (19)
|
0.753
|
Regimen of first-line treatment, n (%)
|
|
|
|
Cisplatin plus Etoposide
|
14 (11)
|
25 (13)
|
|
Cisplatin plus Irinotecan
|
44 (35)
|
43 (23)
|
|
Carboplatin plus Etoposide
|
51 (40)
|
104 (56)
|
|
Other
|
18 (14)
|
15 (8)
|
0.015
|
Subsequent chemotherapy, n (%)
|
|
|
|
Yes
|
95 (75)
|
127 (68)
|
|
No
|
32 (25)
|
60 (32)
|
0.395
|
Relapse pattern of patients treated with subsequent systemic therapy, n (%)
|
|
|
|
Sensitive relapse
|
30 (24)
|
35 (19)
|
|
Refractory relapse
|
65 (51)
|
92 (49)
|
0.515
|
Abbreviations: PS: performance status |
Although the proportion of patients over 75 years old was not significantly different, more older patients were included in the late group. The proportion of patients with stage IV disease or lung metastasis was greater in the late group. Subsequent chemotherapy was administered in 75 patients (75%) of the early group and 127 patients (68%) of the late group.
3.2.2. Efficacy
The ORR of first-line treatment was 78% in the early group and 81% in the late group (Table 2). The MST was 13.0 months (95% CI: 10.5–14.6 months) in the early group, versus 11.8 months (95% CI: 9.4–12.9 months) in the late group (p = 0.18, Figure 2A). The mPFS was 4.9 months (95% CI: 4.2–5.5 months) and 4.9 months (95% CI: 4.6–5.2 months) in the early and late groups (p = 0.87, Figure 2B), respectively.