Table 3.
Multiple treatment comparison for tolerability based on network consistency model (OR > 1 means higher toxicity).
| OR with 95% CI for TRAE | |||||||
|---|---|---|---|---|---|---|---|
| Chemotherapy | 0.65 (0.12, 3.98) | 2.30 (0.21, 34.62) | 1.76 (0.03, 126.31) | 0.55 (0.01, 27.75) | 0.81 (0.01, 47.69) | 0.25 (0.00, 17.55) | – |
| 1.53 (0.25, 8.02) | 1st-generation EGFR-TKIs | 3.44 (0.27, 53.89) | 2.60 (0.06, 123.26) | 0.83 (0.02, 29.44) | 1.22 (0.03, 53.71) | 0.39 (0.01, 17.21) | – |
| 0.44 (0.03, 4.74) | 0.29 (0.02, 3.65) | Afatinib | 0.75 (0.01, 70.02) | 0.24 (0.00, 16.79) | 0.36 (0.00, 26.66) | 0.11 (0.00, 9.70) | – |
| 0.57 (0.01, 30.78) | 0.38 (0.01, 15.78) | 1.33 (0.01, 123.00) | Dacomitinib | 0.31 (0.00, 54.00) | 0.44 (0.00, 84.11) | 0.14 (0.00, 31.06) | – |
| 1.82 (0.04, 92.99) | 1.20 (0.03, 46.01) | 4.20 (0.06, 373.35) | 3.21 (0.02, 766.68) | Osimertinib | 1.52 (0.01, 241.70) | 0.45 (0.00, 95.65) | – |
| 1.23 (0.02, 73.65) | 0.82 (0.02, 32.92) | 2.78 (0.04, 299.27) | 2.26 (0.01, 507.58) | 0.66 (0.00, 120.70) | P + Gefitinib | 0.31 (0.00, 66.39) | – |
| 3.95 (0.06, 259.87) | 2.59 (0.06, 123.07) | 9.06 (0.10, 1110.50) | 6.90 (0.03, 1660.94) | 2.20 (0.01, 449.84) | 3.27 (0.02, 699.85) | PC + Gefitinib | – |
| OR with 95% CI for TRAE 3–5 | |||||||
| Chemotherapy | 0.82 (0.15, 4.51) | 0.86 (0.12, 6.44) | 0.43 (0.01, 18.63) | 2.69 (0.07, 97.08) | 3.31 (0.08, 144.89) | 1.74 (0.04, 69.86) | – |
| 1.22 (0.22, 6.80) | 1st-generation EGFR-TKIs | 1.04 (0.11, 9.97) | 0.53 (0.02, 13.42) | 3.25 (0.12, 89.12) | 4.09 (0.16, 113.60) | 2.12 (0.08, 58.75) | – |
| 1.16 (0.16, 8.42) | 0.96 (0.10, 8.98) | Afatinib | 0.51 (0.01, 26.72) | 3.11 (0.06, 147.43) | 3.87 (0.07, 206.98) | 1.99 (0.04, 107.65) | – |
| 2.31 (0.05, 89.53) | 1.90 (0.07, 48.69) | 1.96 (0.04, 103.13) | Osimertinib | 6.04 (0.05, 682.93) | 7.68 (0.08, 826.09) | 3.97 (0.04, 427.83) | – |
| 0.37 (0.01, 14.74) | 0.31 (0.01, 8.02) | 0.32 (0.01, 16.36) | 0.17 (0.00, 18.93) | P + Gefitinib | 1.24 (0.01, 145.13) | 0.63 (0.01, 72.95) | – |
| 0.30 (0.01, 12.38) | 0.24 (0.01, 6.29) | 0.26 (0.00, 13.73) | 0.13 (0.00, 12.96) | 0.81 (0.01, 83.61) | PC + Gefitinib | 0.50 (0.00, 51.06) | – |
| 0.57 (0.01, 24.92) | 0.47 (0.02, 12.40) | 0.50 (0.01, 27.11) | 0.25 (0.00, 25.74) | 1.58 (0.01, 152.59) | 1.98 (0.02, 202.48) | Erlotinib + Bevacizumab | – |
| OR with 95% CI for Rash | |||||||
| Chemotherapy | 24.34 (11.21, 55.17) | 63.16 (19.35, 211.61) | 59.08 (7.87, 472.09) | 8.86 (1.24, 71.94) | 16.52 (2.03, 141.88) | 18.19 (3.79, 100.96) | 26.96 (4.09, 182.71) |
| 0.04 (0.02, 0.09) | 1st-generation EGFR-TKIs | 2.59 (0.71, 8.87) | 2.41 (0.38, 16.52) | 0.36 (0.05, 2.45) | 0.67 (0.09, 5.07) | 0.75 (0.18, 3.24) | 1.11 (0.20, 6.43) |
| 0.02 (0.00, 0.05) | 0.39 (0.11, 1.41) | Afatinib | 0.94 (0.10, 9.64) | 0.14 (0.01, 1.43) | 0.26 (0.03, 2.89) | 0.29 (0.05, 2.03) | 0.43 (0.05, 3.66) |
| 0.02 (0.00, 0.13) | 0.41 (0.06, 2.65) | 1.06 (0.10, 10.30) | Dacomitinib | 0.15 (0.01, 2.32) | 0.28 (0.02, 4.26) | 0.31 (0.03, 3.27) | 0.46 (0.03, 5.87) |
| 0.11 (0.01, 0.81) | 2.77 (0.41, 18.35) | 7.12 (0.70, 68.39) | 6.68 (0.43, 93.71) | Osimertinib | 1.88 (0.12, 29.86) | 2.08 (0.20, 22.76) | 3.09 (0.22, 40.78) |
| 0.06 (0.01, 0.49) | 1.48 (0.20, 10.61) | 3.79 (0.35, 38.36) | 3.53 (0.23, 55.17) | 0.53 (0.03, 8.33) | P + Gefitinib | 1.10 (0.10, 12.40) | 1.64 (0.13, 21.10) |
| 0.05 (0.01, 0.26) | 1.33 (0.31, 5.41) | 3.44 (0.49, 21.76) | 3.22 (0.31, 33.35) | 0.48 (0.04, 4.97) | 0.91 (0.08, 9.56) | PC + Gefitinib | 1.49 (0.15, 14.39) |
| 0.04 (0.01, 0.24) | 0.90 (0.16, 5.00) | 2.33 (0.27, 20.32) | 2.17 (0.17, 30.75) | 0.32 (0.02, 4.62) | 0.61 (0.05, 7.95) | 0.67 (0.07, 6.69) | Erlotinib + Bevacizumab |
| OR with 95% CI for Diarrhea | |||||||
| Chemotherapy | 5.17 (2.78, 9.68) | 59.57 (24.69, 152.55) | 28.18 (5.69, 134.90) | 5.21 (1.09, 24.07) | 4.57 (0.88, 22.84) | 5.50 (1.63, 19.52) | 6.63 (1.94, 22.59) |
| 0.19 (0.10, 0.36) | 1st-generation EGFR-TKIs | 11.55 (4.57, 31.11) | 5.41 (1.22, 22.83) | 1.01 (0.25, 4.09) | 0.88 (0.20, 3.97) | 1.07 (0.37, 3.27) | 1.28 (0.43, 3.69) |
| 0.02 (0.01, 0.04) | 0.09 (0.03, 0.22) | Afatinib | 0.47 (0.08, 2.58) | 0.09 (0.02, 0.47) | 0.08 (0.01, 0.45) | 0.09 (0.02, 0.39) | 0.11 (0.02, 0.47) |
| 0.04 (0.01, 0.18) | 0.18 (0.04, 0.82) | 2.11 (0.39, 12.76) | Dacomitinib | 0.19 (0.03, 1.47) | 0.16 (0.02, 1.37) | 0.20 (0.03, 1.23) | 0.23 (0.04, 1.49) |
| 0.19 (0.04, 0.91) | 0.99 (0.24, 4.05) | 11.39 (2.13, 62.89) | 5.38 (0.68, 39.83) | Osimertinib | 0.88 (0.11, 6.63) | 1.06 (0.18, 6.29) | 1.26 (0.21, 7.19) |
| 0.22 (0.04, 1.14) | 1.14 (0.25, 5.11) | 13.14 (2.22, 80.71) | 6.08 (0.73, 51.28) | 1.13 (0.15, 9.07) | P + Gefitinib | 1.20 (0.19, 7.92) | 1.45 (0.23, 9.44) |
| 0.18 (0.05, 0.61) | 0.94 (0.31, 2.67) | 10.82 (2.58, 47.57) | 5.06 (0.81, 29.41) | 0.94 (0.16, 5.58) | 0.83 (0.13, 5.18) | PC + Gefitinib | 1.19 (0.25, 5.21) |
| 0.15 (0.04, 0.51) | 0.78 (0.27, 2.31) | 9.07 (2.14, 40.02) | 4.28 (0.67, 25.54) | 0.79 (0.14, 4.75) | 0.69 (0.11, 4.40) | 0.84 (0.19, 3.93) | Erlotinib + Bevacizumab |
| OR with 95% CI for Elevated ALT/AST | |||||||
| Chemotherapy | 1.95 (0.92, 4.24) | 0.76 (0.20, 3.05) | 0.72 (0.10, 5.19) | 0.34 (0.05, 2.48) | 5.02 (0.64, 39.06) | 2.70 (0.61, 12.90) | 1.57 (0.35, 7.28) |
| 0.51 (0.24, 1.08) | 1st-generation EGFR-TKIs | 0.39 (0.10, 1.53) | 0.37 (0.06, 2.22) | 0.17 (0.03, 1.06) | 2.57 (0.38, 17.14) | 1.38 (0.38, 5.31) | 0.81 (0.22, 3.02) |
| 1.31 (0.33, 5.01) | 2.55 (0.65, 10.04) | Afatinib | 0.94 (0.10, 8.92) | 0.44 (0.05, 4.24) | 6.55 (0.62, 67.86) | 3.51 (0.55, 23.38) | 2.06 (0.31, 13.87) |
| 1.39 (0.19, 9.69) | 2.70 (0.45, 16.28) | 1.06 (0.11, 10.03) | Dacomitinib | 0.47 (0.04, 6.08) | 6.94 (0.52, 96.29) | 3.73 (0.41, 36.11) | 2.18 (0.23, 20.72) |
| 2.96 (0.40, 19.88) | 5.76 (0.94, 34.00) | 2.25 (0.24, 20.92) | 2.12 (0.16, 27.11) | Osimertinib | 14.75 (1.08, 196.61) | 7.99 (0.86, 74.33) | 4.68 (0.49, 43.19) |
| 0.20 (0.03, 1.55) | 0.39 (0.06, 2.62) | 0.15 (0.01, 1.62) | 0.14 (0.01, 1.92) | 0.07 (0.01, 0.93) | P + Gefitinib | 0.54 (0.05, 5.50) | 0.31 (0.03, 3.27) |
| 0.37 (0.08, 1.64) | 0.72 (0.19, 2.67) | 0.28 (0.04, 1.83) | 0.27 (0.03, 2.42) | 0.13 (0.01, 1.17) | 1.86 (0.18, 18.30) | PC + Gefitinib | 0.59 (0.09, 3.68) |
| 0.63 (0.14, 2.82) | 1.23 (0.33, 4.61) | 0.49 (0.07, 3.19) | 0.46 (0.05, 4.28) | 0.21 (0.02, 2.03) | 3.18 (0.31, 31.76) | 1.71 (0.27, 11.37) | Erlotinib + Bevacizumab |
CI, confidence interval; EGFR-TKIs, Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors; OR, Odds ratio; P, Pemetrexed; PC, Pemetrexed/Carboplatin; TRAE, Treatment-related Adverse Event; TRAE 3–5, Treatment-related Adverse Event Grade 3–5