| 2.1 Progression‐free survival subgrouped by type of ALK inhibitor |
5 |
1263 |
Hazard Ratio (IV, Random, 95% CI) |
0.39 [0.32, 0.46] |
| 2.1.1 Alectinib |
3 |
697 |
Hazard Ratio (IV, Random, 95% CI) |
0.40 [0.32, 0.49] |
| 2.1.2 Brigatinib |
1 |
275 |
Hazard Ratio (IV, Random, 95% CI) |
0.49 [0.33, 0.73] |
| 2.1.3 Lorlatinib |
1 |
291 |
Hazard Ratio (IV, Random, 95% CI) |
0.28 [0.19, 0.41] |
| 2.2 Progression‐free survival in people with CNS disease |
5 |
800 |
Hazard Ratio (IV, Fixed, 95% CI) |
0.25 [0.19, 0.34] |
| 2.3 Overall adverse events subgrouped by type of ALK inhibitor |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.00 [0.98, 1.01] |
| 2.3.1 Alectinib |
3 |
697 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.99 [0.97, 1.01] |
| 2.3.2 Brigatinib |
1 |
275 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.99 [0.97, 1.01] |
| 2.3.3 Lorlatinib |
1 |
291 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.01 [0.99, 1.04] |
| 2.4 Grade 3/4 adverse events subgrouped by type of ALK inhibitor |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.98 [0.88, 1.08] |
| 2.4.1 Alectinib |
3 |
697 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.73 [0.62, 0.86] |
| 2.4.2 Brigatinib |
1 |
275 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.20 [1.01, 1.42] |
| 2.4.3 Lorlatinib |
1 |
291 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.30 [1.09, 1.56] |
| 2.5 Grade 5 adverse events (excluding progressive disease) subgrouped by type of ALK inhibitor |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.85 [0.49, 1.47] |
| 2.5.1 Alectinib |
3 |
697 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.66 [0.27, 1.62] |
| 2.5.2 Brigatinib |
1 |
275 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.82 [0.35, 1.93] |
| 2.5.3 Lorlatinib |
1 |
291 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.43 [0.41, 4.96] |
| 2.6 Dose intensity |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.6.1 Dose reduction |
4 |
1056 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.27 [1.02, 1.59] |
| 2.6.2 Treatment interruption |
4 |
988 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.83 [0.71, 0.97] |
| 2.6.3 Treatment discontinuation |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.86 [0.63, 1.16] |
| 2.7 Gastrointestinal adverse events |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.7.1 Nausea Any Grade |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.31 [0.26, 0.38] |
| 2.7.2 Vomiting Any Grade |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.28 [0.22, 0.35] |
| 2.7.3 Diarrhoea Any Grade |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.43 [0.37, 0.50] |
| 2.7.4 Constipation Any Grade |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.72 [0.61, 0.84] |
| 2.7.5 Nausea Grade 3 to 4 |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.33 [0.13, 0.81] |
| 2.7.6 Vomiting Grade 3 to 4 |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.20 [0.06, 0.64] |
| 2.7.7 Diarrhoea Grade 3 to 4 |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.61 [0.23, 1.63] |
| 2.7.8 Constipation Grade 3 to 4 |
4 |
960 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.59 [0.08, 4.40] |
| 2.8 Haematological adverse events |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.8.1 Anaemia Grade 3 to 4 |
3 |
801 |
Risk Ratio (M‐H, Fixed, 95% CI) |
2.57 [0.98, 6.77] |
| 2.8.2 Neutropenia Grade 3 to 4 |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.07 [0.03, 0.19] |
| 2.9 Hepatic adverse events |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.9.1 Increased Alanine Aminotransferase Grade 3 to 4 |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.30 [0.18, 0.49] |
| 2.9.2 Increased Aspartate Aminotransferase Grade 3 to 4 |
4 |
1076 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.47 [0.27, 0.82] |
| 2.9.3 Increased Bilirubin Any Grade |
3 |
697 |
Risk Ratio (M‐H, Fixed, 95% CI) |
13.29 [5.48, 32.24] |
| 2.9.4 Increased Bilirubin Grade 3 to 4 |
3 |
697 |
Risk Ratio (M‐H, Fixed, 95% CI) |
3.52 [0.68, 18.37] |
| 2.10 General adverse events |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.10.1 Fatigue Any Grade |
4 |
1075 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.78 [0.62, 0.99] |
| 2.10.2 Loss of Appetite Any Grade |
4 |
960 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.20 [0.13, 0.31] |
| 2.10.3 Oedema Any Grade |
4 |
1076 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.69 [0.57, 0.83] |
| 2.10.4 Rash Any Grade |
5 |
1263 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.81 [1.33, 2.47] |
| 2.11 Overall survival subgrouped by type of ALK inhibitor |
5 |
1263 |
Hazard Ratio (IV, Fixed, 95% CI) |
0.71 [0.56, 0.90] |
| 2.11.1 Alectinib |
3 |
697 |
Hazard Ratio (IV, Fixed, 95% CI) |
0.62 [0.45, 0.85] |
| 2.11.2 Brigatinib |
1 |
275 |
Hazard Ratio (IV, Fixed, 95% CI) |
0.92 [0.59, 1.43] |
| 2.11.3 Lorlatinib |
1 |
291 |
Hazard Ratio (IV, Fixed, 95% CI) |
0.72 [0.41, 1.26] |
| 2.12 Overall survival at 1 year subgrouped by type of ALK inhibitor |
2 |
578 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.98 [0.67, 1.43] |
| 2.12.1 Alectinib |
1 |
303 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.92 [0.55, 1.52] |
| 2.12.2 Brigatinib |
1 |
275 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.06 [0.60, 1.86] |
| 2.13 Overall response rate subgrouped by type of ALK inhibitor |
5 |
1229 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.18 [1.10, 1.25] |
| 2.13.1 Alectinib |
3 |
663 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.14 [1.05, 1.22] |
| 2.13.2 Brigatinib |
1 |
275 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.20 [1.01, 1.41] |
| 2.13.3 Lorlatinib |
1 |
291 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.27 [1.08, 1.49] |
| 2.14 Partial and complete response rate |
5 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.14.1 Partial Response |
5 |
1229 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.15 [1.07, 1.24] |
| 2.14.2 Complete Response |
5 |
1229 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.87 [1.11, 3.16] |
| 2.15 Overall and complete response rate in people with measurable baseline CNS disease |
4 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.15.1 Overall response rate |
4 |
138 |
Risk Ratio (M‐H, Fixed, 95% CI) |
2.45 [1.70, 3.54] |
| 2.15.2 Complete Response Rate |
4 |
138 |
Risk Ratio (M‐H, Fixed, 95% CI) |
8.85 [2.88, 27.20] |
| 2.16 Quality of life: time to deterioration in composite endpoint (cough, dyspnoea, and chest pain) |
1 |
|
Hazard Ratio (IV, Fixed, 95% CI) |
Totals not selected |
