Introduction
Methods
Database search and trial selection
Data extraction
Statistical analyses
Results
Search strategy, results, and study characteristics
Characteristics | Robert et al. [14] | Wardley et al. [24] CHAT study | Valero et al. [15] BCIRG 007 | Baselga et al. [25] | ||||
---|---|---|---|---|---|---|---|---|
Clinicaltrials.gov, number | NS | NCT01038466 | NCT00047255 | NCT00294996 | ||||
Study design | RCT, Phase III | RCT, Phase II | RCT, Phase III | RCT, Phase III | ||||
Recruitment period | 1998–2002 | 2002–2005 | 2001–2004 | 2006–2009 | ||||
No. of countries | 2 | NS | 13 | 12 | ||||
No. of centers | 83 | 43 | 80 | 83 | ||||
Regimen | HPC | HP | HTX | HT | HTC | HT | HPM | HP |
No. of participants | 98 | 98 | 112 | 110 | 132 | 131 | 181 | 182 |
Age (years) Median (range) | 55 (35–81) | 56 (33-83) | 53 (24-82) | 52 (23-78) | 51 (18-75) | 52 (18-75) | 52 (22-79) | 53 (30-76) |
ECOG-PS or KPS, No. (%) | ||||||||
0 or 100 | 59 (60.2) | 60 (61.2) | 112 (100) | 110 (100) | 132 (100) | 131 (100) | 113 (62.4) | 112 (61.5) |
1 or 80–90 | 35 (35.7) | 35 (35.7) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 68 (37.6) | 70 (38.5) |
2 or < 80 | 4 (4.1) | 3 (3.1) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
HER2 status, No. (%) | ||||||||
IHC 3+/FISH+ | 66 (68.4) | 64 (65.3) | 104 (92.9) | 103 (93.6) | 132 (100) | 131 (100) | 177 (97.8) | 179 (98.9) |
IHC 2+ | 32 (31.6) | 33 (34.7) | 8 (7.1) | 7 (6.4) | 0 (0) | 0 (0) | 4 (2.2) | 3 (1.1) |
Hormonal receptor status, No. (%) | ||||||||
ER+ | 51 (52) | 63 (64.3) | 50 (44.6) | 39 (35.5) | NS | NS | NS | NS |
PgR+ | 40 (40.8) | 47 (48.0) | 38 (33.9) | 31 (28.2) | NS | NS | NS | NS |
ER+/PgR+ | NS | NS | 56 (50.0) | 45 (40.9) | 86 (62.5) | 95 (72.5) | 75 (41.4) | 81 (44.5) |
Disease involvement, No. (%) | ||||||||
Visceral | 52 (53.1) | 39 (39.8) | NS | NS | 77 (58.3) | 87 (66.4) | NS | NS |
Lung | NS | NS | 26 (23.2) | 31 (28.2) | NS | NS | 90 (49.7) | 90 (49.5) |
Bone | 42 (42.9) | 37 (37.7) | 26 (23.2) | 28 (25.5) | 44 (33.3) | 55 (41.9) | 64 (35.4) | 71 (39.0) |
Liver | 34 (34.7) | 42 (429) | 15 (13.4) | 22 (20.0) | 65 (49.2) | 67 (51.1) | 70 (38.7) | 80 (44.0) |
Soft tissue | 46 (46.9) | 52 (53.1) | 32 (28.6) | 42 (38.2) | NS | NS | NS | NS |
Othera
| 9 (9.2) | 3 (3.1) | 9 (8.0) | 10 (9.1) | NS | NS | 113 (62.4) | 108 (59.3) |
Prior therapy, No. (%) | ||||||||
Surgery | 78 (79.6) | 74 (75.5) | NS | NS | NS | NS | NS | NS |
Chemotherapy | 48 (49.0) | 45 (45.9) | 55 (49.1) | 55 (50.0) | 73 (55.7) | 71 (53.8) | NS | NS |
Radiotherapy | 37 (37.8) | 41 (41.8) | 49 (43.8) | 52 (47.3) | NS | NS | NS | NS |
Hormonal therapy | 39 (40.8) | 50 (51.0) | 35 (31.3) | 36 (32.7) | 48 (36.4) | 35 (26.7) | NS | NS |
Anthracycline | NS | NS | 49 (43.8) | 49 (44.5) | 43 (32.6) | 43 (32.8) | 59 (32.6) | 60 (33.0) |
Taxane | NS | NS | NS | NS | 12 (9.1) | 14 (10.7) | 14 (7.7) | 12 (6.6) |
Trastuzumab | NS | NS | NS | NS | NS | NS | 2 (1.1) | 4 (1.1) |
No prior chemotherapy | NS | NS | NS | NS | 59 (44.7) | 57 (43.5) | NS | NS |
Outcomes | ||||||||
Follow-up (months) | 52 | 26 (median) | 84 | 44 (median) | ||||
Median response duration (months) | 13 | 11 | 15.9 | 13.4 | 10.7 | 9.4 | 18.1 | 15.3 |
Median OS (months) | 35.7 | 32.2 | 46.0 | 40.2 | 37.4 | 37.1 | 33.6 | 29.0 |
Median PFS (months) | 10.7 | 7.1 | 17.9 | 12.8 | NR | NR | 16.1 | 14.5 |
Primary and secondary end points | PFS, OS, ORR, DCR, Safety | PFS, OS, ORR, DCR, Safety | OS, ORR, DCR, Safety | PFS, OS, ORR, DCR, Safety |
Efficacy
ORR did not significantly differ between the groups
Outcomes | No. of participants | Relative effect | Risk difference | GRADE | |||
---|---|---|---|---|---|---|---|
Ratio (95% CI) |
P value |
I
2
| (95% CI) | Quality | Importance | ||
Complete response | 671 (14, 15, 24) | RR 1.28 (0.90 to 1.82) | 0.176 | 37.5% | 4% (− 2 to 9%) | ⊕⊕ΟΟ Lowa,b
| Important |
Partial response | 671 (14, 15, 24) | RR 1.07 (0.83 to 1.38) | 0.601 | 61.9% | 3% (− 9 to 16%) | ⊕⊕ΟΟ Lowa,b
| Important |
Overall response | 1034 (14, 15, 24, 25) | RR 1.07 (0.98 to 1.17) | 0.157 | 41.3% | 4% (− 2 to 10%) | ⊕⊕⊕Ο Moderatea
| Critical |
Stable disease | 671 (14, 15, 24) | RR 1.02 (0.78 to 1.32) | 0.910 | 40.0% | 0.4% (− 6 to 7%) | ⊕⊕ΟΟ Lowa,b
| Important |
Disease control | 671 (14, 15, 24) | RR 1.05 (0.96 to 1.15) | 0.282 | 65.8% | 5% (− 4 to 13%) | ⊕⊕ΟΟ Lowa,c
| Important |
Progressive disease | 671 (14, 15, 24) | RR 0.59 (0.34 to 1.04) | 0.066 | 22.1% | − 5% (− 11 to 1%) | ⊕⊕ΟΟ Lowa,b
| Important |
Median duration of response | 1034 (14, 15, 24, 25) | MR 1.17 (1.10 to 1.25) | < 0.0001 | 0.0% | – | ⊕⊕⊕Ο Moderatea
| Important |
Progression-free survival | 771 (14, 24, 25) | HR 0.69 (0.63 to 0.75) | < 0.0001 | 31.3% | – | ⊕⊕⊕Ο Moderatea
| Critical |
Median progression-free survival | 771 (14, 24, 25) | MR 1.32 (1.09 to 1.60) | 0.004 | 85.7% | – | ⊕⊕ΟΟ Lowa,c
| Important |
Overall survival | 1034 (14, 15, 24, 25) | HR 0.90 (0.88 to 0.92) | < 0.0001 | 0.0% | – | ⊕⊕⊕Ο Moderatea
| Critical |
Median overall survival | 1034 (14, 15, 24, 25) | MR 1.11 (1.04 to 1.18) | 0.001 | 9.1% | – | ⊕⊕⊕Ο Moderatea
| Important |