Table 1.
Main characteristics and results of the 22 studies included in the meta-analysis.
| Article source | EGFR situation | Trial name | Lines of therapy | EGFR-TKI intervention | Control treatment | Total patients | Median age (years) | Median follow-up (months) | Overall HR (95% CI) | Sex of HR (95% CI) | Smoking of HR (95% CI) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Male | Female | Never | Ever | ||||||||||
| Thatcher et al. (15) | Unknown | ISEL | >1 | Gefitinib | Placebo | 1,692 | 62/61 | 7.2 | 0.89 (0.77–1.02) | 0.91 (0.78-1.06) | 0.77 (0.60-0.97) | 0.67 (0.49-0.91) | 0.92 (0.80-1.05) |
| Tsao et al. (16) | Unknown | BR.21 | >1 | Erlotinib | Placebo | 731 | 62/59 | NR | 0.70 (0.58–0.85) | 0.76 (0.62–0.94) | 0.80 (0.59–1.07) | 0.42 (0.28–0.64) | 0.87 (0.71–1.05) |
| Kim et al. (17) | Unknown | INTEREST | >1 | Gefitinib | Docetaxel | 1,433 | 61/60 | 7.6 | 1.02 (0.91–1.15) | 1.08 (0.95–1.24) | 0.95 (0.78–1.17) | 0.93 (0.70–1.23) | 1.05 (0.92–1.19) |
| Maruyama et al. (18) | Unknown | V-15-32 | >1 | Gefitinib | Docetaxel | 489 | NR | 21 | 1.12 (0.89–1.40) | 1.10 (0.83–1.43) | 1.23 (0.81–1.84) | 0.93 (0.58–1.48) | 1.13 (0.87–1.45) |
| Cappuzzo et al. (19) | Unknown | SATURN | >1 | Erlotinib | Placebo | 889 | 60/60 | 11.4/11.5 | 0.81 (0.70–0.95) | 0.88 (0.74–1.05) | 0.64 (0.46–0.91) | 0.69 (0.45–1.05) | 0.84 (0.71–0.99) |
| Fukuoka et al. (20) | Unknown | IPASS | 1 | Gefitinib | Carboplatin plus paclitaxel | 1,217 | 57/57 | 17 | 0.90 (0.79–1.02) | 0.77 (0.59–1.02) | 0.93 (0.81–1.08) | 0.90 (0.78–1.03) | 0.99 (0.62–1.60) |
| Lee et al. (21) | Unknown | TOPICAL | 1 | Erlotinib | Placebo | 670 | 77/77 | NR | 0.94 (0.81–1.10) | Female vs. male 0.81 (0.59–1.01) |
Never vs. ever 0.64 (0.36–1.14) |
||
| Pérol et al. (22) | Unknown | IFCT-GFPC 0502 |
>1 | Erlotinib | Observation | 310 | 56.4/59.8 | 25.6 | 0.87 (0.68–1.13) | 0.88 (0.66–1.18) | 0.89 (0.52–1.53) | 0.83 (0.34–2.01) | 0.88 (0.68–1.15) |
| Kelly et al. (23) | Wild-type | PDX-012 | >1 | Erlotinib | Pralatrexate | 201 | 62/63 | NR | 1.19 (0.88–1.64) | 1.08 (0.75–1.56) | 1.64 (0.92–2.94) | NR | NR |
| Miller et al. (24) | Unknown | LUX-Lung 1 | >1 | Afatinib | Placebo | 585 | 58/59 | NR | 1.08 (0.86–1.35) | 1.17 (0.83–1.65) | 1.02 (0.76–1.37) | 1.20 (0.90–1.61) | 0.43 (0.31–0.61) |
| Ciuleanu et al. (25) | Unknown | TITAN | >1 | Erlotinib | Docetaxel or pemetrexed | 424 | 59/59 | 27.9/24.8 | 0.96 (0.78–1.19) | 0.86 (0.67–1.10) | 1.23 (0.78–1.94) | 0.86 (0.49–1.51) | 0.93 (0.78–1.11) |
| Garassino et al. (26) | Wild-type | TAILOR | >1 | Erlotinib | Docetaxel | 219 | 66/67 | 33 | 1.27 (0.95–1.69) | 1.18 (0.84–1.67) | 1.47 (0.84–2.56) | 1.69 (0.89–3.23) | 1.12 (0.81–1.54) |
| Inoue et al. (27) | Mutation | NEJ002 | 1 | Gefitinib | Carboplatin plus paclitaxel | 228 | NR | 23 | 0.89 (0.63–1.24) | 0.92 (0.53–1.61) | 0.88 (0.57–1.35) | 0.88 (0.57–1.37) | 0.98 (0.58–1.65) |
| Ellis et al. (28) | Unknown | NCIC CTG BR.26 |
>1 | Dacomitinib | Placebo | 720 | 63.5/65.5 | 23.4/24.4 | 1.00 (0.83–1.21) | NR | NR | 0.74 (0.56–0.98) | 1.13 (0.91–1.40) |
| Gregorc et al. (29) | Unknown | PROSE | >1 | Erlotinib | Pemetrexed or docetaxel | 263 | 66/64 | 32.4 | 1.15 (0.83–1.59) | Female vs. male 0.90 (0.64–1.27) |
Never vs. ever 0.80 (0.51–1.27) |
||
| Li et al. (30) | Wild-type | NR | >1 | Erlotinib | Pemetrexed | 123 | 54.3/55.1 | 14.7 | 1.01 (0.66–1.54) | 1.24 (0.73–2.11) | 0.64 (0.31–1.33) | 0.81 (0.34–1.90) | 1.10 (0.68–1.80) |
| Karachaliou et al. (31) | Unknown | EURTAC | 1 | Erlotinib | Cisplatin plus docetaxel or gemcitabine | 97 | NR | 49.4 | 0.71 (0.45–1.12) | Female vs. male 0.96 (0.59–1.56) | NR | NR | |
| Zhou et al. (32) | Mutation | OPTIMAL | 1 | Erlotinib | Gemcitabine plus carboplatin | 154 | 57/59 | 25.9 | 1.19 (0.83–1.71) | 1.31 (0.75–2.31) | 1.20 (0.74–1.93) | 1.44 (0.93–2.24) | 0.85 (0.44–1.64) |
| Wu et al. (33) | Mutation | ENSURE | 1 | Erlotinib | Gemcitabine plus cisplatin | 217 | 57.5/56 | 28.9/27.1 | 0.91 (0.63–1.31) | 0.86 (0.45–1.64) | 0.92 (0.59–1.44) | 0.99 (0.65–1.52) | 0.68 (0.32–1.43) |
| Yang et al. (34) | Mutation | LUX-Lung 3 and LUX-Lung 6 | 1 | Afatinib | Pemetrexed-cisplatin or gemcitabine-cisplatin | 631 | 60/59 | 41/33 | 0.81 (0.66–0.99) | 0.71 (0.51–0.99) | 0.84 (0.65–1.09) | 0.72 (0.57–0.92) | 1.02 (0.69–1.50) |
| Zhao et al. (35) | Unknown | INFORM | >1 | Gefitinib | Placebo | 296 | 55/55 | 17.8 | 0.88 (0.68–1.14) | 0.89 (0.64–1.24) | 0.93 (0.61–1.41) | 0.94 (0.65–1.35) | 0.82 (0.57–1.19) |
| Shi et al. (36) | Mutation | CONVINCE | 1 | Icotinib | Cisplatin plus pemetrexed | 285 | 56 | 39.6 | 1.03 (0.76–1.39) | 1.19 (0.69–2.04) | 0.96 (0.67–1.39) | 1.02 (0.72–1.45) | 1.20 (0.64–2.27) |
EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; HR, hazard ratio; CI, confidence interval; NR, none reported.