Table 1.
Subgroups: long term outcomes | No of comparisons analysed | R2 (95% CI) | Slope of regression line | STE | F test for homogeneity of slopes | |
---|---|---|---|---|---|---|
Disease-free survival | Overall survival | |||||
Main analyses | ||||||
Disease-free survival | 67 | 0.14 (0.00 to 0.29) | −0.27 | 5.19 | - | |
Overall survival | 59 | 0.08 (0.00 to 0.22) | −0.20 | - | ||
Subgroups analyses | ||||||
pCR definition: | ||||||
Breast only | ||||||
Disease-free survival | 14 | 0.02 (0.00 to 0.19) | −0.08 | - | 0.23 | 0.35 |
Overall survival | 14 | 0.01 (0.00 to 0.12) | −0.06 | - | ||
Breast and lymph nodes: | ||||||
Disease-free survival | 52 | 0.15 (0.00 to 0.34) | −0.32 | 4.44 | ||
Overall survival | 44 | 0.10 (0.00 to 0.28) | −0.26 | - | ||
Treatment arms | ||||||
Antracycline and taxane based v antracycline based regimens: | ||||||
Disease-free survival | 10 | 0.002 (0.00 to 0.06) | 0.02 | - | 0.03 | 0.17 |
Overall survival | 9 | 0.01 (0.00 to 0.14) | −0.03 | - | ||
Intensified/dose dense v standard dose regimens: | ||||||
Disease-free survival | 10 | 0.62 (0.18 to 1.00) | −0.49 | 2.43 | ||
Overall survival | 10 | 0.45 (0.00 to 0.99) | −0.38 | 4.88 | ||
Chemotherapy plus anti-HER2 targeted treatment: | ||||||
Disease-free survival | 17 | 0.46 (0.08 to 0.85) | −0.80 | 2.74 | ||
Overall survival | 13 | 0.31 (0.00 to 0.78) | −0.69 | - | ||
Capecitabine-containing v standard regimens | ||||||
Disease-free survival | 6 | 0.21 (0.00 to 1.00) | −0.64 | - | ||
Overall survival | 6 | 0.64 (0.00 to 1.00) | −1.05 | - | ||
Chemotherapy plus bevacizumab: | ||||||
Disease-free survival | 5 | 0.06 (0.00 to 0.72) | 0.52 | - | ||
Overall survival | 5 | 0.10 (0.00 to 0.87) | 1.00 | - | ||
Other comparisons: | ||||||
Disease-free survival | 19 | 0.02 (0.00 to 0.14) | −0.08 | - | ||
Overall survival | 16 | 0.02 (0.00 to 0.15) | −0.08 | - | ||
Biological features of disease | ||||||
Triple negative: | ||||||
Disease-free survival | 19 | 0.42 (0.05 to 0.79) | −0.63 | 2.24 | 0.56 | 0.33 |
Overall survival | 16 | 0.17 (0.00 to 0.55) | −0.37 | - | ||
HER2 positive: | ||||||
Disease-free survival | 25 | 0.37 (0.05 to 0.69) | −0.80 | 2.43 | ||
Overall survival | 18 | 0.002 (0.00 to 0.05) | 0.08 | - | ||
Time-to-recurrence endpoint definition: | ||||||
Disease free survival | ||||||
Disease-free survival | 38 | 0.03 (0.00 to 0.15) | −0.11 | - | 0.03 | 0.34 |
Overall survival | 37 | 0.02 (0.00 to 0.10) | −0.09 | - | ||
Event-free survival | ||||||
Event-free survival | 14 | 0.40 (0.00 to 0.85) | −0.86 | 2.05 | ||
Overall survival | 10 | 0.25 (0.00 to 0.81) | −0.34 | - | ||
Others | ||||||
Others | 15 | 0.39 (0.00 to 0.82) | −0.44 | 4.39 | ||
Overall survival | 12 | 0.29 (0.00 to 0.79) | −0.38 | - | ||
Sensitivity analyses | ||||||
Delta-pCR as surrogate endpoint: | ||||||
Disease-free survival | 67 | 0.24 (0.06 to 0.42) | −1.83 | 0.22 | - | |
Overall survival | 59 | 0.13 (0.00 to 0.30) | −1.38 | 0.31 | ||
Randomised controlled trials with sample size <200 patients excluded: | ||||||
Disease-free survival | 56 | 0.13 (0.00 to 0.30) | −0.26 | - | ||
Overall survival | 49 | 0.06 (0.00 to 0.20) | −0.18 | - | ||
Trial sample size as weight in the regression model: | ||||||
Disease-free survival | 67 | 0.14 (0.00 to 0.30) | −0.34 | 5.00 | ||
Overall survival | 59 | 0.09 (0.00 to 0.23) | −0.26 | - | ||
Inverse of variance of log of pCR relative risk as weight in regression model: | ||||||
Disease-free survival | 67 | 0.25 (0.07 to 0.44) | −0.69 | 2.32 | ||
Overall survival | 59 | 0.14 (0.00 to 0.31) | −0.43 | 3.29 | ||
Randomised controlled trials with <24 months of follow-up excluded: | ||||||
Disease-free survival | 63 | 0.13 (0.00 to 0.29) | −0.25 | 6.05 | ||
Overall survival | 57 | 0.07 (0.00 to 0.20) | −0.19 | - |
STE=surrogate threshold effect; pCR=pathological complete response; anti-HER2=anti-human epidermal growth factor 2.