Summary of findings 2. Next‐generation ALK inhibitor compared to crizotinib for advanced anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer.
| Next‐generation ALK inhibitor compared to crizotinib for advanced anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer | |||||
| Patient or population: advanced anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer Intervention: next‐generation ALK inhibitor Comparison: crizotinib | |||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | |
| Risk with crizotinib | Risk with next‐generation ALK inhibitor | ||||
| Progression‐free survival: overall population | Study population | HR 0.39 (0.32 to 0.46) | 1263 (5 RCTs) | ⊕⊕⊕⊕ HIGH | |
| 0 per 1000 | 0 per 1000 | ||||
| Progression‐free survival in people with central nervous system disease | Study population | HR 0.25 (0.19 to 0.34) | 406 (5 RCTs) | ⊕⊕⊕⊕ HIGH | |
| 0 per 1000 | 0 per 1000 | ||||
| Overall adverse events | Study population | RR 1.00 (0.98 to 1.01) | 1263 (5 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | |
| 990 per 1000 | 990 per 1000 (970 to 1000) | ||||
| Grade 5 adverse events (excluding progressive disease) | Study population | RR 0.85 (0.49 to 1.47) | 1263 (5 RCTs) | ⊕⊕⊝⊝ LOW 2 | |
| 42 per 1000 | 36 per 1000 (21 to 62) | ||||
| Overall survival | Study population | HR 0.71 (0.56 to 0.90) | 1263 (5 RCTs) | ⊕⊕⊕⊝ MODERATE 3 | |
| 0 per 1000 | 0 per 1000 | ||||
| Overall response rate | Study population | RR 1.18 (1.10 to 1.25) | 1229 (5 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | |
| 691 per 1000 | 816 per 1000 (760 to 864) | ||||
| Health‐related quality of life: time to deterioration in composite endpoint (cough, dyspnoea, and chest pain) | Study population | HR 1.10 (0.72 to 1.68) | 303 (1 RCT) | ⊕⊝⊝⊝ VERY LOW 1 4 5 | |
| 0 per 1000 | 0 per 1000 | ||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HR: hazard ratio; RCT: randomised controlled trial; RR: risk ratio | |||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | |||||
1Downgraded one level for risk of bias, as assessors for adverse events were not blinded to treatment allocation, which might have affected this outcome. 2Downgraded two levels for imprecision, as there were fewer than 100 events, and the summary statistic includes both gain and no effect. 3Downgraded one level for inconsistency, as trials found both a positive effect and no effect. 4Downgraded one level for imprecision, as there were fewer than 400 participants (303). 5Downgraded one level for indirectness, as result was based on population from only one trial.