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. 2022 Jan 7;2022(1):CD013453. doi: 10.1002/14651858.CD013453.pub2

Comparison 1. ALK inhibitor versus chemotherapy.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1.1 Progression‐free survival subgrouped by line of treatment 6   Hazard Ratio (IV, Fixed, 95% CI) 0.45 [0.40, 0.52]
1.1.1 1st line 3   Hazard Ratio (IV, Fixed, 95% CI) 0.47 [0.40, 0.56]
1.1.2 2nd or subsequent line 3   Hazard Ratio (IV, Fixed, 95% CI) 0.43 [0.36, 0.52]
1.2 Progression‐free survival subgrouped by type of ALK inhibitor 6   Hazard Ratio (IV, Fixed, 95% CI) 0.45 [0.40, 0.52]
1.2.1 Alectinib 1   Hazard Ratio (IV, Fixed, 95% CI) 0.20 [0.12, 0.33]
1.2.2 Crizotinib 3   Hazard Ratio (IV, Fixed, 95% CI) 0.45 [0.38, 0.53]
1.2.3 Ceritinib 2   Hazard Ratio (IV, Fixed, 95% CI) 0.52 [0.43, 0.64]
1.3 Progression‐free survival in people with CNS disease 6 581 Hazard Ratio (IV, Fixed, 95% CI) 0.51 [0.41, 0.62]
1.4 Overall adverse events subgrouped by line of treatment 5 1404 Risk Ratio (M‐H, Fixed, 95% CI) 1.01 [1.00, 1.03]
1.4.1 1st line 2 719 Risk Ratio (M‐H, Fixed, 95% CI) 1.02 [1.00, 1.03]
1.4.2 2nd or subsequent line 3 685 Risk Ratio (M‐H, Fixed, 95% CI) 1.01 [0.98, 1.04]
1.5 Overall adverse events subgrouped by type of ALK inhibitor 5 1404 Risk Ratio (M‐H, Fixed, 95% CI) 1.01 [1.00, 1.03]
1.5.1 Alectinib 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 0.91 [0.76, 1.09]
1.5.2 Crizotinib 2 690 Risk Ratio (M‐H, Fixed, 95% CI) 1.01 [0.99, 1.02]
1.5.3 Ceritinib 2 607 Risk Ratio (M‐H, Fixed, 95% CI) 1.03 [1.01, 1.05]
1.6 Grade 3/4 adverse events subgrouped by line of treatment 5 1404 Risk Ratio (M‐H, Fixed, 95% CI) 1.09 [1.00, 1.19]
1.6.1 1st line 2 719 Risk Ratio (M‐H, Fixed, 95% CI) 1.12 [1.00, 1.26]
1.6.2 2nd or subsequent line 3 685 Risk Ratio (M‐H, Fixed, 95% CI) 1.06 [0.94, 1.20]
1.7 Grade 3/4 adverse events subgrouped by type of ALK inhibitor 5 1404 Risk Ratio (M‐H, Fixed, 95% CI) 1.09 [1.00, 1.19]
1.7.1 Alectinib 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 0.75 [0.42, 1.32]
1.7.2 Crizotinib 2 690 Risk Ratio (M‐H, Fixed, 95% CI) 0.99 [0.85, 1.16]
1.7.3 Ceritinib 2 607 Risk Ratio (M‐H, Fixed, 95% CI) 1.20 [1.09, 1.31]
1.8 Total Grade 5 adverse events subgrouped by line of treatment 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 3.33 [2.02, 5.48]
1.8.1 1st line 3 926 Risk Ratio (M‐H, Fixed, 95% CI) 3.60 [1.78, 7.29]
1.8.2 2nd or subsequent line 3 685 Risk Ratio (M‐H, Fixed, 95% CI) 3.05 [1.50, 6.18]
1.9 Grade 5 adverse events (excluding progressive disease) subgrouped by line of treatment 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 2.03 [0.89, 4.66]
1.9.1 1st line 3 926 Risk Ratio (M‐H, Fixed, 95% CI) 2.31 [0.77, 6.93]
1.9.2 2nd or subsequent line 3 685 Risk Ratio (M‐H, Fixed, 95% CI) 1.67 [0.47, 5.98]
1.10 Grade 5 adverse events (excluding progressive disease) subgrouped by ALK inhibitor 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 2.03 [0.89, 4.66]
1.10.1 Alectinib 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 0.16 [0.01, 3.94]
1.10.2 Crizotinib 3 897 Risk Ratio (M‐H, Fixed, 95% CI) 2.10 [0.69, 6.41]
1.10.3 Ceritinib 2 607 Risk Ratio (M‐H, Fixed, 95% CI) 4.32 [0.74, 25.29]
1.11 Dose intensity 5   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.11.1 Treatment reductions 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 0.36 [0.09, 1.54]
1.11.2 Treatment interruption 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 2.11 [0.64, 6.91]
1.11.3 Treatment discontinuation 5 1235 Risk Ratio (M‐H, Fixed, 95% CI) 1.03 [0.73, 1.45]
1.12 Gastrointestinal adverse events 6   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.12.1 Nausea any 5 1504 Risk Ratio (M‐H, Fixed, 95% CI) 1.31 [1.18, 1.44]
1.12.2 Nausea Grade 3 to 4 5 1504 Risk Ratio (M‐H, Fixed, 95% CI) 2.55 [1.19, 5.47]
1.12.3 Vomiting any 5 1504 Risk Ratio (M‐H, Fixed, 95% CI) 1.90 [1.66, 2.16]
1.12.4 Vomiting Grade 3 to 4 5 1504 Risk Ratio (M‐H, Fixed, 95% CI) 1.38 [0.73, 2.63]
1.12.5 Diarrhoea any 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 3.64 [3.12, 4.25]
1.12.6 Diarrhoea Grade 3 to 4 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 2.89 [1.45, 5.77]
1.12.7 Constipation any 6 1610 Risk Ratio (M‐H, Fixed, 95% CI) 1.36 [1.16, 1.60]
1.12.8 Constipation Grade 3 to 4 6 1610 Risk Ratio (M‐H, Fixed, 95% CI) 2.44 [0.67, 8.95]
1.13 Haematological adverse events 6   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.13.1 Anaemia Grade 3 to 4 5 1380 Risk Ratio (M‐H, Fixed, 95% CI) 0.22 [0.12, 0.40]
1.13.2 Neutropenia Grade 3 to 4 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 0.52 [0.40, 0.68]
1.13.3 Thrombocytopenia Grade 3 to 4 3 781 Risk Ratio (M‐H, Fixed, 95% CI) 0.13 [0.04, 0.43]
1.14 Hepatic adverse events 4   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.14.1 Increased alanine aminotransferase Grade 3 to 4 3 954 Risk Ratio (M‐H, Fixed, 95% CI) 9.52 [5.19, 17.46]
1.14.2 Increased aspartate aminotransferase Grade 3 to 4 3 954 Risk Ratio (M‐H, Fixed, 95% CI) 8.12 [3.75, 17.60]
1.14.3 Increased bilirubin any grade 2 338 Risk Ratio (M‐H, Fixed, 95% CI) 2.39 [0.35, 16.21]
1.14.4 Increased bilirubin Grade 3 to 4 1 231 Risk Ratio (M‐H, Fixed, 95% CI) Not estimable
1.15 General any grade adverse events 6   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.15.1 Fatigue 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.69, 0.95]
1.15.2 Loss of appetite 5 1504 Risk Ratio (M‐H, Fixed, 95% CI) 1.12 [0.96, 1.31]
1.15.3 Oedema 3 897 Risk Ratio (M‐H, Fixed, 95% CI) 3.14 [2.39, 4.13]
1.15.4 Rash any grade 3 921 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.57, 1.15]
1.16 Overall survival subgrouped by line of treatment 6 1611 Hazard Ratio (IV, Fixed, 95% CI) 0.84 [0.72, 0.97]
1.16.1 1st line 3 926 Hazard Ratio (IV, Fixed, 95% CI) 0.78 [0.62, 0.97]
1.16.2 2nd or subsequent line 3 685 Hazard Ratio (IV, Fixed, 95% CI) 0.89 [0.73, 1.09]
1.17 Overall survival subgrouped by type of ALK inhibitor 6   Hazard Ratio (IV, Fixed, 95% CI) 0.84 [0.72, 0.97]
1.17.1 Alectinib 1   Hazard Ratio (IV, Fixed, 95% CI) 0.91 [0.49, 1.69]
1.17.2 Crizotinib 3   Hazard Ratio (IV, Fixed, 95% CI) 0.83 [0.69, 0.99]
1.17.3 Ceritinib 2   Hazard Ratio (IV, Fixed, 95% CI) 0.85 [0.64, 1.11]
1.18 Overall survival at 1 year 2   Risk Ratio (M‐H, Fixed, 95% CI) Totals not selected
1.19 Overall response rate by line of treatment 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 2.43 [2.16, 2.75]
1.19.1 1st line 3 926 Risk Ratio (M‐H, Fixed, 95% CI) 2.03 [1.79, 2.30]
1.19.2 2nd or subsequent line 3 685 Risk Ratio (M‐H, Fixed, 95% CI) 4.08 [3.03, 5.48]
1.20 Overall response rate subgrouped by type of ALK inhibitor 6 1611 Risk Ratio (M‐H, Fixed, 95% CI) 2.43 [2.16, 2.75]
1.20.1 Alectinib 1 107 Risk Ratio (M‐H, Fixed, 95% CI) 13.12 [1.86, 92.68]
1.20.2 Crizotinib 3 897 Risk Ratio (M‐H, Fixed, 95% CI) 2.09 [1.83, 2.40]
1.20.3 Ceritinib 2 607 Risk Ratio (M‐H, Fixed, 95% CI) 3.12 [2.45, 3.97]
1.21 Partial and complete response rate 5   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.21.1 Partial response 5 1380 Risk Ratio (M‐H, Fixed, 95% CI) 2.30 [2.03, 2.59]
1.21.2 Complete response 5 1380 Risk Ratio (M‐H, Fixed, 95% CI) 2.70 [0.80, 9.14]
1.22 Overall and complete response rate in people with measurable baseline CNS disease 3   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.22.1 Overall response rate 3 108 Risk Ratio (M‐H, Fixed, 95% CI) 4.88 [2.18, 10.95]
1.22.2 Complete response rate 2 71 Risk Ratio (M‐H, Fixed, 95% CI) 1.56 [0.32, 7.57]
1.23 Quality of life: time to deterioration in composite endpoint (cough, dyspnoea, and chest pain) 5 1504 Hazard Ratio (IV, Fixed, 95% CI) 0.52 [0.44, 0.60]
1.23.1 Crizotinib 3 897 Hazard Ratio (IV, Fixed, 95% CI) 0.52 [0.43, 0.61]
1.23.2 Ceritinib 2 607 Hazard Ratio (IV, Fixed, 95% CI) 0.51 [0.38, 0.70]