Background
Methods
Patients
Study design
Criteria for therapy initiation and dose reduction
Premedication and supportive therapy
Concomitant therapy
Surgery and postoperative therapy
Endpoints
Histological assessment criteria
Target sample size
Randomization
Statistical analysis
Results
Patients
Number of patients (%) | Total | FEC-TC | TC-FEC | TC |
---|---|---|---|---|
193 | 65 | 63 | 65 | |
Age (years) | ||||
Median (range) | 48 (26–69) | 50 (26–69) | 48 (28–68) | 50 (30–68) |
cT | ||||
cT1c | 27 (14.0) | 8 (12.3) | 9 (14.3) | 10 (15.4) |
cT2 | 140 (72.5) | 49 (75.4) | 42 (66.7) | 49 (75.4) |
cT3 | 26 (13.5) | 8 (12.3) | 12 19.0) | 6 (9.2) |
Primary tumor (mm) by MRI or CT | ||||
Median (range) | 29 (9–82) | 30 (10–70) | 29 (10–70) | 27 (9–82) |
cN | ||||
cN0 | 95 (49.2) | 34 (52.3) | 30 (47.6) | 31 (47.7) |
cN1 | 98 (50.8) | 31 (47.7) | 33 (52.4) | 34 (52.3) |
TNM | ||||
I | 8 (4.1) | 2 (3.1) | 3 (4.8) | 3 (4.6) |
IIA | 97 (50.3) | 35 (53.8) | 28 (44.4) | 34 (52.3) |
IIB | 71 (36.8) | 23 (35.4) | 25 (39.7) | 23 (35.4) |
IIIA | 17 (8.8) | 5 (7.7) | 7 (11.1) | 5 (7.7) |
Menopause status | ||||
Premenopausal | 119 (61.7) | 37 (56.9) | 41 (65.1) | 41 (63.1) |
Postmenopausal | 74 (38.3) | 28 (43.1) | 22 34.9) | 24 (36.9) |
Planed surgery | ||||
Breast-conserving | 114 (59.1) | 37 (56.9) | 36 (57.1) | 41(63.1) |
Mastectomy | 79 (40.9) | 28 (43.1) | 2742.9) | 24(36.9) |
Histology | ||||
IDC | 182 (94.3) | 58 (89.2) | 60 (95.2) | 64 (98.4) |
ILC | 9 (4.7) | 6 (9.2) | 2 (3.2) | 1 (1.5) |
Micropapillary | 1 (0.5) | 1 (1.5) | 0 | 0 |
Medullary | 1 (0.5) | 0 | 1 (1.6) | 0 |
IHC: ER | ||||
≥ 80% | 138 (71.5) | 45 (69.2) | 48 (76.2) | 45 (69.2) |
50%–79% | 37 (19.2) | 14 (21.5) | 10 (15.9) | 13 (20.0) |
10–49% | 13 (6.7) | 4 (6.2) | 4 (6.3) | 5 (7.7) |
1–9% | 5 (2.6) | 2 (3.1) | 1 (1.6) | 2 (3.1) |
IHC: PgR | ||||
≥ 80% | 73 (37.8) | 20 (30.8) | 26 (41.3) | 27 (41.5) |
50–79% | 37 (19.2) | 18 (27.7) | 9 (14.3) | 10 (15.4) |
10–49% | 38 (19.7) | 13 (20.0) | 15 (23.8) | 10 (15.4) |
1–9% | 23 (11.9) | 9 (23.8) | 4 (6.3) | 10 (15.4) |
0% | 22 (11.4) | 5 (7.7) | 9 (14.3) | 8 (12.3) |
HER2 | ||||
IHC: 0 | 72 (37.3) | 25 (38.5) | 4 (6.3) | 23 (35.4) |
IHC: 1+ | 79 (40.9) | 26 (40.0) | 24 (38.1) | 28 (43.1) |
IHC 2+ or untested and FISH (−) | 42 (21.8) | 14 (21.5) | 25 (39.7) | 14 (21.5) |
Efficacy
Total (N = 193) | FEC-TC (N = 65) | TC-FEC (N = 63) | TC (N = 65) | Comparative p-value across three groups | |
---|---|---|---|---|---|
SpCR, n (%) | 16 (8) | 6 (9) | 4 (7) | 6 (10) | 0.848 |
pCRinv, n (%) | 11 (6) | 3 (5) | 4 (7) | 4 (6) | 0.861 |
Near pCR, n (%) | 2 (1) | 0 (0) | 1 (2) | 1 (2) | 0.548 |
CpCR (SpCR + pCRinv), n (%) | 27 (14) | 9 (14) | 8 (13) | 10 (16) | 0.901 |
QpCR (CpCR + near pCR, n (%) | 29 (15) | 9 (14) | 9 (15) | 11 (18) | 0.876 |
CpCR + ypN0, n (%) | 21 (11) | 6 (9) | 5 (8) | 10 (16) | 0.321 |
QpCR + ypN0, n (%) | 23 (12) | 6 (9) | 6 (10) | 11 (18) | 0.280 |
Total | FEC-TC group | TC-FEC group | TC group | |
---|---|---|---|---|
n (%) | 193 Patients | 65 Patients | 63 Patients | 65 Patients |
CR | 21 (10.9) | 8 (12.3) | 3 (4.8) | 10 (15.4) |
PR | 121 (62.7) | 39 (60.0) | 43 (68.3) | 39 (60.0) |
CR + PR | 142 (73.6) | 47 (72.3) | 46 (73.0) | 49 (75.4) |
SD | 40 (20.7) | 14 (21.5) | 15 (23.8) | 11 (16.9) |
PD | 1 (0.5) | 0 | 0 | 1 (1.5) |
NE | 10 (5.2) | 4 (6.2) | 2 (3.2) | 4 (6.2) |
Pre-chemotherapy plan for surgical procedure | Surgery performed | Total (N = 193) | FEC-TC (N = 65) | TC-FEC (N = 63) | TC (N = 65) | Comparative p-value across three groups |
---|---|---|---|---|---|---|
Lumpectomy | Lumpectomy | 83 (74.1%) | 24 (64.9%) | 23 (65.7%) | 36 (90.0%) | |
Mastectomy | 29 (25.9%) | 13 (35.1%) | 12 (34.3%) | 4 (10.0%) | p = 0.017 | |
No surgery | 2 | 0 | 1 | 1 | ||
Total | 114 | 37 | 36 | 41 | ||
Mastectomy | Lumpectomy | 24 (30.8%) | 9 (32.1%) | 5 (18.5%) | 10 (43.5%) | p = 0.160 |
Mastectomy | 54 (69.2%) | 19 (67.9%) | 22 (81.5%) | 13 (56.5%) | ||
No surgery | 1 | 0 | 0 | 1 | ||
Total | 79 | 28 | 27 | 24 | ||
Lumpectomy | 107 (56.3%) | 33 (50.8%) | 28 (45.2%) | 46 (73.0%) | p = 0.007 |
Adverse events
Total (N = 193) | FEC-TC (N = 65) | TC-FEC (N = 63) | TC (N = 65) | |||||
---|---|---|---|---|---|---|---|---|
All grades | Grades 3/4 | All grades | Grades 3/4 | All grades | Grades 3/4 | All grades | Grades 3/4 | |
Subjective and objective symptoms | ||||||||
Allergic reaction, hypersensitivity | 16 (8.3) | 2 (1.0) | 3 (4.6) | 0 (0.0) | 10 (15.9) | 1 (1.6) | 3 (4.7) | 1 (1.6) |
Febrile neutropenia | 35 (18.2) | 35 (18.2) | 12 (18.5) | 12 (18.5) | 14 (22.2) | 14 (22.2) | 9 (13.8) | 9 (13.8) |
Infection accompanied by grade 3/4 neutropenia | 2 (1.0) | 2 (1.0) | 0 | 0 | 2 (3.2) | 2 (3.2) | 0 | 0 |
Fatigue (asthenia/inactivity/malaise) | 106 (55.2) | 1 (0.5) | 38 (58.5) | 0 | 34 (54.0) | 1 (1.6) | 34 (53.1) | 0 |
Skin eruption, desquamation | 96 (50.0) | 2 (1.0) | 20 (30.8) | 0 | 36 (57.1) | 0 | 40 (62.5) | 2 (3.1) |
Anorexia | 86 (43.0) | 1 (0.5) | 31 (47.7) | 1 (1.5) | 28 (44.4) | 0 | 27 (42.2) | 0 |
Nausea | 94 (49.0) | 1 (0.5) | 33 (50.8) | 1 (1.5) | 40 (63.5) | 0 | 21 (32.8) | 0 |
Stomatitis | 84 (43.8) | 2 (1.0) | 30 (46.2) | 0 | 29 (46.0) | 1 (1.6) | 25 (39.1) | 1 (1.6) |
Edema in the trunk or genitals | 33 (17.5) | 26 (13.8) | 3 (4.7) | 1 (1.6) | 13 (21.0) | 13 (21.0) | 17 (26.9) | 12 (19.4) |
Stomatitis | 84 (43.8) | 2 (1.0) | 30 (46.2) | 0 | 29 (46.0) | 1 (1.6) | 25 (39.1) | 1 (1.6) |
Hematological tests | ||||||||
White blood cell count | 145 (75.5) | 90 (46.9) | 42 (64.6) | 12 (18.5) | 59 (93.7) | 43 (68.3) | 44 (68.8) | 35 (54.7) |
Neutrophil count | 111 (58.4) | 91 (47.9) | 22 (33.8) | 14 (21.5) | 51 (82.3) | 41 (66.1) | 38 (60.3) | 36 (57.1) |
Hemoglobin | 121 (63.0) | 1 (0.5) | 45 (69.2) | 0 | 46 (73.0) | 1 (1.6) | 30 (46.9) | 0 (0.0) |
Platelet count | 27 (14.1) | 1 (0.5) | 11 (16.9) | 0 (0.0) | 10 (15.9) | 0 (0.0) | 6 (9.4) | 1 (1.6) |
ALT | 71 (37.0) | 3 (1.6) | 23 (35.4) | 0 (0.0) | 23 (36.5) | 2 (3.2) | 25 (39.1) | 1 (1.6) |