Summary of findings 1. Trastuzumab‐containing regimens for early breast cancer.
| Summary of findings for the main comparison. Overview: efficacy and safety outcomes for patient groups at different risks | ||||||
| Patient or population: HER2‐positive early breast cancer patients Settings: Early breast cancer Intervention: Trastuzumab | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | Trastuzumab | |||||
| Overall survival (OS) Follow‐up: median 36 months | Low | HR 0.66 (0.57 to 0.77) | 9945 (8 studies) | ⊕⊕⊕⊕ high1 | ||
| 100 per 1000 | 67 per 1000 (58 to 78) | |||||
| Moderate | ||||||
| 300 per 1000 | 210 per 1000 (184 to 240) | |||||
| High | ||||||
| 500 per 1000 | 367 per 1000 (326 to 414) | |||||
| Disease free survival (DFS) Follow‐up: median 36 months | Low | HR 0.6 (0.5 to 0.71) | 9935 (8 studies) | ⊕⊕⊕⊕ high1 | ||
| 100 per 1000 | 61 per 1000 (51 to 72) | |||||
| Moderate | ||||||
| 300 per 1000 | 193 per 1000 (163 to 224) | |||||
| High | ||||||
| 500 per 1000 | 340 per 1000 (293 to 389) | |||||
| Congestive heart failure (CHF) | Low | RR 5.11 (3 to 8.72)2 | 10281 (8 studies) | ⊕⊕⊕⊕ high1 | ||
| 5 per 1000 | 26 per 1000 (15 to 44)2 | |||||
| Moderate | ||||||
| 20 per 1000 | 102 per 1000 (60 to 174)2 | |||||
| High | ||||||
| 50 per 1000 | 256 per 1000 (150 to 436)2 | |||||
| Left ventricular ejection fraction decline (LVEF) | Low | RR 1.83 (1.36 to 2.47)2 | 7939 (7 studies) | ⊕⊕⊕⊝ moderate1,3 | ||
| 5 per 1000 | 9 per 1000 (7 to 12)2 | |||||
| Moderate | ||||||
| 30 per 1000 | 55 per 1000 (41 to 74)2 | |||||
| High | ||||||
| 50 per 1000 | 92 per 1000 (68 to 124)2 | |||||
| Brain metastasis as first site of relapse | 13 per 1000 | 23 per 1000 (17 to 32)2 | RR 1.75 (1.29 to 2.38)2 | 6881 (5 studies) | ⊕⊕⊝⊝ low4 | |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95%) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; HR: hazard ratio. | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 We did not downgrade although there was some concern about publication bias for some study arms. 2 CI 90%. 3 There is substantial heterogeneity among studies included in the analysis of LVEF decrease (I2 = 70%). 4 The analysis for brain metastasis is limited by the design of trials which considered only the first site of relapse. High risk of bias and the number of events was less than 150. Overall we decided to downgrade by two levels when considering these issues.