Summary of findings for the main comparison. Taxane followed by anthracyclines compared to anthracyclines followed by taxane in neoadjuvant therapy for early breast cancer.
| Taxane followed by anthracyclines compared to anthracyclines followed by taxane in neoadjuvant therapy for early breast cancer | ||||||
| Patient or population: neoadjuvant therapy for early breast cancer Setting: outpatient Intervention: taxane followed by anthracyclines Comparison: anthracyclines followed by taxane | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with anthracyclines followed by taxane | Risk with taxane followed by anthracyclines | |||||
| Overall survival (follow‐up: up to 5 years) | 3‐year risk of deatha | HR 0.80 (0.60 to 1.08) | 947 (2 RCTs) | ⊕⊕⊕⊝ Moderateb | — | |
| 702 per 1000 | 620 per 1000 (516 to 729) | |||||
| Disease‐free survival (follow‐up: up to 5 years) | 3‐year risk of recurrencea | HR 0.84 (0.65 to 1.09) | 828 (1 RCT) | ⊕⊕⊕⊝ Moderatec | — | |
| 616 per 1000 | 552 per 1000 (463 to 648) | |||||
|
Pathological complete response (no invasive cancer in breast or axilla) (follow‐up: up to 5 years for 2 studies; unreported in 2 studies) |
Study population | RR 1.15 (0.96 to 1.38) | 1280 (4 RCTs) | ⊕⊕⊕⊕ Highd | — | |
| 228 per 1000 | 262 per 1000 (219 to 314) | |||||
|
Adverse events: neutropenia (grade 3/4) (follow‐up: up to 6 months based on number of chemotherapy cycles) |
Study population | RR 1.25 (0.86 to 1.82) | 280 (1 RCT) | ⊕⊕⊕⊝ Moderatee | — | |
| 254 per 1000 | 317 per 1000 (218 to 462) | |||||
|
Adverse events: neurotoxicity (grade 3/4) (follow‐up: up to 5 or 6 months based on number of chemotherapy cycles) |
Study population | RR 0.95 (0.55 to 1.65) | 1108 (2 RCTs) | ⊕⊕⊝⊝ Lowf | — | |
| 45 per 1000 | 43 per 1000 (25 to 75) | |||||
|
Treatment adherence (defined as dose reduction) (follow‐up: up to 6 months based on number of chemotherapy cycles) |
Study population | RR 0.81 (0.59 to 1.11) | 280 (1 RCT) | ⊕⊕⊕⊝ Moderateg | — | |
| 399 per 1000 | 323 per 1000 (235 to 442) | |||||
| Quality of life | — | — | — | — | Not measured | |
| *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 | ||||||
aThe baseline risk in the anthracycline followed by taxane group was based on risk estimates provided in Neo‐TAnGo 2014 (Figure 2D for overall survival; Figure 2B for disease‐free survival). bThe number of events did not meet the optimal information size (approximately 120 events in total in one study) and only one study reported follow‐up of five years for overall survival. Therefore, we downgraded by one level for both imprecision and indirectness. cThe optimal information size was not met (as per GRADE guidance; Guyatt 2011). Therefore, we downgraded by one level for imprecision only. dWe did not downgrade for imprecision as the optimal information size was met. eThe confidence intervals were very wide, indicating no effect and appreciable benefit and harm with taxanes first. Therefore, we downgraded by one level for imprecision. fThe confidence intervals were very wide and the impact of unblinding on the assessment of neurotoxicity was unclear. Therefore we downgraded by one level for imprecision and one level for risk of bias. gThe optimal information size was not met (as per GRADE guidance; Guyatt 2011), and the impact of unblinding on treatment adherence was unclear. Therefore, we downgraded by one level only for imprecision and risk of bias. We did not think that risk of bias was very serious due to the design of the studies whereby participants received both treatment drugs but in a different order; therefore, we deducted 0.5 levels for risk of bias.