Background
Methods
Study design and participants
Procedures
Study end points
Statistical analyses
Results
Patient characteristics
Characteristic | Asian | Non-Asian | ||
---|---|---|---|---|
EVE + TRAS + PAC | PBO + TRAS + PAC | EVE + TRAS + PAC | PBO + TRAS + PAC | |
n = 198 |
n = 105 |
n = 282 |
n = 134 | |
Median age, years (range) | 53.0 (23–75) | 51.0 (29–82) | 55.0 (26–86) | 52.0 (19–77) |
Race, n (%) | ||||
Asian | 198 (100%) | 105 (100%) | 0 | 0 |
Black | 0 | 0 | 26 (9.2) | 12 (9.0) |
White | 0 | 0 | 214 (75.9) | 97 (72.4) |
Native American | 0 | 0 | 3 (1.1) | 0 |
Other non-Asian | 0 | 0 | 39 (13.8) | 25 (18.7) |
Ethnicity, n (%) | ||||
Chinese | 145 (73.2) | 75 (71.4) | 0 | 0 |
Indiana
| 1 (0.5%) | 0 | 0 | 0 |
Japanese | 27 (13.6) | 15 (14.3) | 0 | 0 |
Other Asian | 25 (12.6) | 15 (14.3) | 0 | 0 |
Hispanic/Latino | 0 | 0 | 78 (27.7) | 34 (25.4) |
Other non-Asian | 0 | 0 | 204 (72.3) | 100 (74.6) |
Current disease status, n (%) | ||||
Locally advanced | 10 (5.1) | 7 (6.7) | 24 (8.5) | 9 (6.7) |
Metastatic | 188 (94.9) | 98 (93.3) | 258 (91.5) | 125 (93.3) |
Site of metastasis, n (%) | ||||
Visceral | 139 (70.2) | 65 (61.9) | 199 (70.6) | 104 (77.6) |
Lung | 91 (46.0) | 43 (41.0) | 126 (44.7) | 60 (44.8) |
Liver | 66 (33.3) | 36 (34.3) | 111 (39.4) | 74 (55.2) |
Lung and liver | 27 (13.6) | 17 (16.2) | 45 (16.0) | 34 (25.4) |
Bone | 85 (42.9) | 54 (51.4) | 125 (44.3) | 63 (47.0) |
Bone only | 9 (4.5) | 5 (4.8) | 11 (3.9) | 2 (1.5) |
Others | 142 (71.7) | 77 (73.3) | 196 (69.5) | 99 (73.9) |
ECOG PS, n (%) | ||||
0 | 121 (61.1) | 64 (61.0) | 157 (55.7) | 84 (62.7) |
1 | 77 (38.9) | 41 (39.0) | 125 (44.3) | 50 (37.3) |
ER and PgR status, n (%) | ||||
ER and PgR negative (HR–) | 85 (42.9) | 47 (44.8) | 123 (43.6) | 56 (41.8) |
ER and PgR negative (HR+) | 112 (56.6) | 57 (54.3) | 159 (56.4) | 78 (58.2) |
Not assessable | 0 | 1 (1.0) | 0 | 0 |
Missing | 1 (0.5) | 0 | 0 | 0 |
Dose intensity and exposure
Overall population | HR– subpopulation | |||||||
---|---|---|---|---|---|---|---|---|
Asian | Non-Asian | Asian | Non-Asian | |||||
EVE + TRAS + PAC | PBO + TRAS + PAC | EVE + TRAS + PAC | PBO + TRAS + PAC | EVE + TRAS + PAC | PBO + TRAS + PAC | EVE + TRAS + PAC | PBO + TRAS + PAC | |
n = 196 |
n = 104 |
n = 276 |
n = 134 |
n = 85 |
n = 47 |
n = 121 |
n = 56 | |
Relative dose intensity, median (range) | ||||||||
EVE | 0.51 (0.03–1.00) | 0.95 (0.01–1.00) (PBO) | 0.57 (0.05–1.00) | 0.97 (0.12–1.00) (PBO) | 0.50 (0.03–1.00) | 0.95 (0.13–1.00) (PBO) | 0.61 (0.05–1.00) | 0.96 (0.29–1.00) (PBO) |
TRAS | 0.96 (0.28–1.08) | 0.97 (0.75–1.03) | 0.96 (0.08–1.16) | 0.96 (0.41–1.06) | 0.98 (0.49–1.08) | 0.97 (0.78–1.02) | 0.97 (0.37–1.12) | 0.96 (0.61–1.03) |
PAC | 0.65 (0.01–1.09) | 0.72 (0.08–1.22) | 0.72 (0.04–1.40) | 0.84 (0.11–1.25) | 0.65 (0.01–1.08) | 0.82 (0.08–1.22) | 0.73 (0.11–1.40) | 0.79 (0.13–1.00) |
Duration of exposure, median (range), weeks | ||||||||
EVE | 42.14 (0.6–241.7) | 59.93 (2.0–240.7) | 40.00 (1.1–233.1) | 40.71 (1.1–207.4) | 45.86 (0.6–210.4) | 41.29 (2.1–221.1) | 44.71 (1.4–233.1) | 38.50 (1.1–207.4) |
TRAS | 58.07 (3.0–242.3) | 64.07 (3.0–241.0) | 45.00 (1.0–233.7) | 40.43 (1.0–208.0) | 58.29 (3.0–211.0) | 41.00 (3.0–221.9) | 49.86 (2.0–233.7) | 38.50 (4.0–208.0) |
PAC | 36.50 (1.0–201.0) | 37.14 (1.0–230.0) | 27.07 (1.0–155.1) | 30.00 (1.0–174.0) | 35.00 (1.0–201.0) | 35.00 (1.0–190.0) | 28.86 (2.0–141.7) | 27.00 (1.0–167.9) |
Efficacy
Safety
Adverse event, % | Asian | Non-Asian | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
EVE + TRAS + PAC | PBO + TRAS + PAC | EVE + TRAS + PAC | PBO + TRAS + PAC | |||||||||
n = 196 |
n = 104 |
n = 276 |
n = 134 | |||||||||
Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 | |
Stomatitis | 62.2 | 6.6 | 0.0 | 31.7 | 0.0 | 0.0 | 69.6 | 16.7 | 0.0 | 32.8 | 2.2 | 0.0 |
Diarrhea | 48.0 | 6.1 | 0.0 | 40.4 | 3.8 | 0.0 | 62.7 | 11.2 | 0.0 | 51.5 | 4.5 | 0.0 |
Rash | 43.4 | 1.0 | 0.0 | 24.0 | 1.0 | 0.0 | 38.0 | 0.4 | 0.0 | 17.9 | 0.0 | 0.0 |
Neutropenia | 42.3 | 27.6 | 4.6 | 26.9 | 17.3 | 3.8 | 34.1 | 16.7 | 2.9 | 23.1 | 5.2 | 4.5 |
Alopecia | 41.3 | 0.0 | 0.0 | 41.3 | 0.0 | 0.0 | 50.7 | 0.4 | 0.0 | 61.2 | 0.0 | 0.0 |
Pyrexia | 39.8 | 0.5 | 0.0 | 26.0 | 1.0 | 0.0 | 38.4 | 2.2 | 0.0 | 26.9 | 1.5 | 0.0 |
Cough | 38.3 | 0.5 | 0.0 | 35.6 | 0.0 | 0.0 | 41.3 | 0.4 | 0.0 | 30.6 | 1.5 | 0.0 |
Fatigue | 33.2 | 3.1 | 0.0 | 29.8 | 1.9 | 0.0 | 36.6 | 6.2 | 0.0 | 40.3 | 3.0 | 0.0 |
Epistaxis | 29.1 | 0.0 | 0.0 | 10.6 | 0.0 | 0.0 | 36.2 | 0.0 | 0.0 | 23.1 | 0.0 | 0.0 |
Edema peripheral | 28.6 | 0.0 | 0.0 | 17.3 | 1.0 | 0.0 | 36.2 | 1.4 | 0.0 | 29.9 | 0.0 | 0.0 |
ALT increased | 28.1 | 5.1 | 0.0 | 26.9 | 6.7 | 0.0 | 15.6 | 6.5 | 0.0 | 11.9 | 3.0 | 0.7 |
Nasopharyngitis | 27.0 | 0.0 | 0.0 | 30.8 | 1.9 | 0.0 | 12.7 | 0.0 | 0.0 | 11.2 | 0.0 | 0.0 |
Nausea | 26.0 | 0.5 | 0.0 | 25.0 | 1.9 | 0.0 | 37.3 | 1.1 | 0.0 | 41.8 | 0.0 | 0.0 |
Hypoesthesia | 23.5 | 3.1 | 0.0 | 26.9 | 1.9 | 0.0 | 5.4 | 0.0 | 0.0 | 5.2 | 0.0 | 0.0 |
Mouth ulceration | 23.0 | 1.0 | 0.0 | 10.6 | 0.0 | 0.0 | 5.4 | 0.7 | 0.0 | 1.5 | 0.0 | 0.0 |
Decreased appetite | 22.4 | 1.0 | 0.0 | 16.3 | 0.0 | 0.0 | 23.9 | 1.4 | 0.0 | 13.4 | 0.0 | 0.0 |
Myalgia | 22.4 | 0.0 | 0.0 | 25.0 | 1.0 | 0.0 | 12.0 | 0.0 | 0.0 | 14.2 | 0.0 | 0.0 |
Neutrophil count decreased | 21.9 | 11.2 | 3.6 | 20.2 | 12.5 | 1.9 | 0.4 | 0.4 | 0.0 | 1.5 | 0.0 | 0.0 |
Headache | 20.9 | 1.0 | 0.0 | 18.3 | 1.9 | 0.0 | 33.0 | 0.4 | 0.0 | 37.3 | 0.0 | 0.0 |
Leukopenia | 20.4 | 8.7 | 0.5 | 14.4 | 5.8 | 1.0 | 11.6 | 4.0 | 0.4 | 6.7 | 3.0 | 0.0 |
Neurotoxicity | 19.9 | 0.0 | 0.0 | 22.1 | 1.0 | 0.0 | 0.4 | 0.0 | 0.0 | 0.7 | 0.0 | 0.0 |
Insomnia | 19.9 | 0.0 | 0.0 | 11.5 | 0.0 | 0.0 | 13.8 | 0.0 | 0.0 | 20.1 | 0.0 | 0.0 |
Vomiting | 19.4 | 1.0 | 0.0 | 20.2 | 1.9 | 0.0 | 30.1 | 1.1 | 0.0 | 25.4 | 3.0 | 0.0 |
Dizziness | 18.9 | 2.0 | 0.5 | 15.4 | 0.0 | 0.0 | 13.4 | 0.0 | 0.0 | 14.9 | 1.5 | 0.0 |
Weight decreased | 18.9 | 0.5 | 0.0 | 4.8 | 0.0 | 0.0 | 22.5 | 2.2 | 0.0 | 5.2 | 0.0 | 0.0 |
AST increased | 18.4 | 2.6 | 0.0 | 14.4 | 3.8 | 0.0 | 13.8 | 4.0 | 0.7 | 9.0 | 0.7 | 0.7 |
Dyspnea | 17.3 | 2.0 | 0.0 | 1.0 | 0.0 | 0.0 | 29.3 | 4.3 | 0.7 | 17.2 | 1.5 | 0.0 |
Constipation | 16.3 | 0.0 | 0.0 | 18.3 | 0.0 | 0.0 | 25.0 | 0.0 | 0.0 | 23.1 | 0.0 | 0.0 |
Peripheral sensory neuropathy | 15.8 | 0.5 | 0.0 | 18.3 | 0.0 | 0.0 | 11.6 | 0.7 | 0.0 | 12.7 | 1.5 | 0.0 |
Pruritus | 15.8 | 0.5 | 0.0 | 8.7 | 0.0 | 0.0 | 12.0 | 0.4 | 0.0 | 11.2 | 0.0 | 0.0 |
WBC count decreased | 15.3 | 9.7 | 0.5 | 12.5 | 7.7 | 0.0 | 1.1 | 0.7 | 0.0 | 0.7 | 0.0 | 0.0 |
Oropharyngeal pain | 15.3 | 0.0 | 0.0 | 11.5 | 0.0 | 0.0 | 15.9 | 0.0 | 0.0 | 14.2 | 0.0 | 0.0 |
Arthralgia | 13.8 | 0.0 | 0.0 | 11.5 | 0.0 | 0.0 | 19.2 | 1.4 | 0.0 | 21.6 | 1.5 | 0.0 |
Anemia | 13.3 | 5.6 | 1.0 | 7.7 | 1.9 | 0.0 | 43.5 | 10.5 | 1.4 | 22.4 | 3.0 | 0.0 |
Hypercholesterolemia | 12.8 | 0.5 | 0.0 | 7.7 | 0.0 | 0.0 | 22.5 | 1.4 | 0.0 | 11.2 | 0.0 | 0.0 |
Neuropathy peripheral | 12.8 | 0.5 | 0.0 | 15.4 | 3.8 | 0.0 | 40.2 | 6.2 | 0.0 | 31.3 | 5.2 | 0.0 |
Pneumoniaa
| 12.2 | 1.5 | 1.0 | 4.8 | 0.0 | 0.0 | 7.6 | 2.9 | 0.0 | 3.7 | 0.0 | 0.0 |
Pneumonitisa
| 12.2 | 2.0 | 0.0 | 2.9 | 0.0 | 0.0 | 19.2 | 5.4 | 1.4 | 5.2 | 0.7 | 0.0 |
Hyperglycemiaa
| 11.7 | 4.6 | 1.0 | 1.9 | 1.0 | 0.0 | 14.1 | 5.8 | 0.7 | 8.2 | 1.5 | 0.0 |
Pain in extremity | 11.7 | 0.5 | 0.0 | 12.5 | 0.0 | 0.0 | 22.5 | 1.4 | 0.4 | 18.7 | 0.0 | 0.0 |
Back pain | 11.2 | 1.0 | 0.0 | 11.5 | 1.0 | 0.0 | 18.1 | 1.1 | 0.0 | 21.6 | 3.0 | 0.0 |
Hypertension | 11.2 | 2.6 | 0.0 | 11.5 | 1.0 | 0.0 | 17.8 | 2.2 | 0.0 | 10.4 | 2.2 | 0.0 |
Hypokalemia | 10.7 | 5.1 | 0.5 | 2.9 | 2.9 | 0.0 | 17.0 | 7.2 | 2.2 | 3.7 | 0.0 | 0.0 |
Abdominal pain | 10.7 | 1.5 | 0.0 | 9.6 | 0.0 | 0.0 | 18.1 | 0.4 | 0.0 | 14.2 | 0.0 | 0.0 |
Asthenia | 9.2 | 2.0 | 0.0 | 8.7 | 0.0 | 0.0 | 26.8 | 1.4 | 0.0 | 23.9 | 1.5 | 0.0 |
Urinary tract infection | 6.6 | 0.5 | 0.0 | 3.8 | 0.0 | 0.0 | 17.0 | 1.4 | 0.0 | 9.7 | 0.0 | 0.0 |