Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Table 2
Pooled results of survival and response rate in the and TKI alone groups.
Endpoints
Study numbers
vs. TKI alone
HR/RR (95% CI)
value
PFS
Median (95% CI), months
HR (95% CI)
PFS (INV) (overall)
6
17.9 (16.3–19.5) vs. 11.9 (11.1–12.8)
0.596 (0.516–0.689)
<0.01
PFS (IRC) (overall)
2
17.3 (15.3–19.2) vs. 11.2 (10.0–12.4)
0.612 (0.506–0.740)
<0.01
PFS in EGFR 19del
4
18.4 (16.5–20.3) vs. 12.21 (11.0–13.4)
0.611 (0.551–0.677)
<0.01
PFS in EGFR L858R
4
18.0 (15.5–20.4) vs. 10.76 (9.4–12.1)
0.580 (0.468–0.718)
<0.01
PFS in BM
2
12.7 (9.7–NR) vs. 11.2 (8.8–14.7)
0.529 (0.364–0.770)
0.001
PFS in no-BM
2
18 (15.4–NR) vs. 15.1 (11.1–16.1)
0.606 (0.462–0.797)
<0.01
PFS in ECOG PS 0
3
NR
0.548 (0.417–0.721)
<0.01
PFS in ECOG PS 1
3
NR
0.646 (0.507–0.786)
<0.01
PFS2 (overall)
2
NR
0.756 (0.612–0.934)
0.010
PFS in male
4
NR
0.553 (0.433-0.706)
0.003
PFS in female
5
NR
0.621 (0.519-0.742)
<0.01
PFS in stage IIIB
2
NR
0.393 (0.125-1.234)
0.110
PFS in stage IV
3
NR
0.600 (0.505-0.713)
<0.01
PFS in recurrence
3
NR
0.440 (0.239-0.811)
0.008
PFS in never-smoker
2
NR
0.645 (0.495-0.840)
0.001
OS
Median (95% CI), months
HR (95% CI)
value
OS (overall)
4
46.1 vs. 47.4
0.933 (0.743–1.172)
0.551
OS in EGFR 19del
3
46.6 vs. NC
0.736 (0.352–1.539)
0.416
OS in EGFR L858R
2
48.0 vs. 39.7
0.808 (0.543–1.204)
0.295
OSR
% (95% CI)
RR (95% CI)
value
1-year OSR (overall)
3
93.4% (90.6–96.2%) vs. 93.4% (90.7–96.2%)
1.068 (0.607–1.880)
0.818
2-year OSR (overall)
2
79.2% (69.9–88.5%) vs. 78.3% (73.6–82.9%)
0.876 (0.641–1.196)
0.404
ORR
% (95% CI)
RR (95% CI)
value
ORR (overall)
6
77.3% (74–80.5%) vs. 74.4% (71–77.8%)
0.884 (0.769–1.106)
0.083
ORR in EGFR 19del
2
76.9% (70.7–80%) vs. 67.2% (60.2–74.1%)
0.774 (0.641–0.936)
0.008
ORR in EGFR L858R
2
67.9% (60.6–75.3%) vs. 64.9% (57.6–72.3%)
0.937 (0.759–1.104)
0.435
TKI: tyrosine kinase inhibitor; : angiogenic inhibitors combined with TKI; 19del: exon 19 deletion; PFS: progression-free survival; PFS2: time from randomization to second disease progression or death from any cause; OS: overall survival; OSR: OS rate; ORR: objective response rate; DCR: disease control rate; NR; not reported; NC: not calculated; ECOG: Eastern Cooperative Oncology Group; PS: performance status; BM; INV: investigator-assessed; IRC: independent review committee-assessed; HR: Hazard ratios; RR: Relative risk ratios; 95% CI: 95% confidence intervals.
