Introduction
Methods
Study design and patients
Procedures
Outcomes
Statistical analysis
Results
Patient disposition and baseline characteristics
Nivolumab 3 mg/kg (N = 152) | Placebo (N = 74) | |
---|---|---|
Male | 111 (73) | 57 (77) |
Female | 41 (27) | 17 (23) |
Age (years) median (min, max) | 65 (20, 83) | 66 (28, 79) |
Patients aged < 65 years | 68 (45) | 28 (38) |
Country | ||
Japan | 152 | 74 |
Korea | – | – |
Taiwan | – | – |
Eastern Cooperative Oncology Group performance status | ||
0 | 64 (42) | 31 (42) |
1 | 88 (58) | 43 (58) |
Organs with metastases | ||
< 2 | 43 (28) | 22 (30) |
≥ 2 | 109 (72) | 52 (70) |
Site of metastases | ||
Lymph node | 129 (85) | 60 (81) |
Peritoneum | 28 (18) | 15 (20) |
Liver | 35 (23) | 17 (23) |
Lung | 11 (7) | 4 (5) |
Pleura | 1 (1) | 1 (1) |
Adrenal glands | 0 | 2 (3) |
Bone | 3 (2) | 3 (4) |
Other | 8 (5) | 7 (10) |
Previous treatment regimensa | ||
2 | 11 (7) | 3 (4) |
3 | 57 (38) | 26 (35) |
≥ 4 | 84 (55) | 45 (61) |
Previous therapies | ||
Any | 152 (100) | 74 (100) |
Pyrimidine analogs | 152 (100) | 74 (100) |
Platinum | 138 (91) | 71 (96) |
Taxanes | 150 (99) | 72 (97) |
Irinotecan | 137 (90) | 70 (95) |
Ramucirumab | 34 (22) | 21 (28) |
Previous gastrectomy | ||
No | 56 (37) | 31 (42) |
Yes | 96 (63) | 43 (58) |
Exposure and subsequent pharmacotherapy in the Japanese subpopulation
Efficacy in the Japanese subpopulation
Overall survival
Nivolumab 3 mg/kg (N = 152) | Placebo (N = 74) | |
---|---|---|
OS rate, % (95% CI) | ||
At 3 months | 76.2 (68.6–82.2) | 58.9 (46.8–69.2) |
At 6 months | 47.1 (38.9–54.8) | 34.2 (23.7–45.1) |
At 9 months | 35.8 (28.2–43.4) | 20.5 (12.2–30.4) |
At 12 months | 27.8 (21.0–35.1) | 15.1 (8.0–24.2) |
At 18 months | 19.5 (13.0–27.0) | 9.0 (3.8–17.1) |
PFS rate, % (95% CI) | ||
At 3 months | 35.0 (27.3–42.8) | 13.9 (6.9–23.2) |
At 6 months | 19.0 (13.0–25.9) | 6.2 (2.0–13.7) |
At 9 months | 13.9 (8.8–20.2) | 6.2 (2.0–13.7) |
At 12 months | 9.4 (5.2–15.0) | 3.1 (0.6–9.5) |
At 18 months | 5.2 (2.1–10.5) | 1.5 (0.1–7.3) |
Progression-free survival
Response
Nivolumab (N = 129) | Placebo (N = 60) | |
---|---|---|
Best overall response, n (%) | ||
CR | 0 | 0 |
PR | 18 (14.0) | 0 |
SD | 40 (31.0) | 14 (23.3) |
PD | 61 (47.3) | 40 (66.7) |
NE | 10 (7.8) | 6 (10.0) |
ORR | ||
ORR (CR + PR) | 18 (14.0) | 0 |
(95% CI)a | (8.5, 21.2) | (0.0, 6.0) |
p valueb | 0.0023* | |
DCR | ||
DCR (CR + PR + SD) | 58 (45.0) | 14 (23.3) |
(95% CI)a | (36.2–54.0) | (13.4–36.0) |
p valueb | 0.0037* |
PD-L1 expression status
Safety in the Japanese subpopulation
Adverse event, n (%) | Nivolumab (N = 152) | Placebo (N = 72) | ||
---|---|---|---|---|
Any grade | Grade 3/4 | Any grade | Grade 3/4 | |
All | 86 (56.6) | 24 (15.8) | 22 (30.6) | 7 (9.7) |
Pruritus | 17 (11.2) | 0 | 1 (1.4) | 0 |
Diarrhea | 14 (9.2) | 2 (1.3) | 2 (2.8) | 0 |
Malaise | 12 (7.9) | 0 | 6 (8.3) | 0 |
Fatigue | 11 (7.2) | 1 (0.7) | 4 (5.6) | 2 (2.8) |
Decreased appetite | 10 (6.6) | 3 (2.0) | 4 (5.6) | 1 (1.4) |
Rash | 10 (6.6) | 0 | 2 (2.8) | 0 |
Nausea | 10 (6.6) | 0 | 1 (1.4) | 0 |
Additional treatment-related adverse events of special interest | ||||
Interstitial lung disease | 6 (3.9) | 1 (0.7) | 0 | 0 |
Rash maculo-papular | 5 (3.3) | 0 | 0 | 0 |
Colitis | 2 (1.3) | 1 (0.7) | 0 | 0 |
Hypopituitarism | 1 (0.7) | 1 (0.7) | 0 | 0 |
Pneumonitis | 1 (0.7) | 1 (0.7) | 0 | 0 |
Hyperthyroidism | 1 (0.7) | 0 | 0 | 0 |
Thyroid disorder | 1 (0.7) | 0 | 0 | 0 |
Hepatic function abnormal | 0 | 0 | 2 (2.8) | 1 (1.4) |
Acute hepatic failure | 0 | 0 | 1 (1.4) | 1 (1.4) |
Acute hepatitis | 0 | 0 | 0 | 0 |
Autoimmune thyroiditis | 0 | 0 | 0 | 0 |
Efficacy analysis of patients with prior ramucirumab treatment
With prior ramucirumab treatment | Without prior ramucirumab treatment | |||
---|---|---|---|---|
Nivolumab (N = 27) | Placebo (N = 19) | Nivolumab (N = 102) | Placebo (N = 41)a | |
Best overall response, n (%) | ||||
CR | 0 | 0 | 0 | 0 |
PR | 6 (22.2) | 0 | 12 (11.8) | 0 |
SD | 9 (33.3) | 4 (21.1) | 31 (30.4) | 10 (24.4) |
PD | 7 (25.9) | 13 (68.4) | 54 (52.9) | 27 (65.9) |
NE | 5 (18.5) | 2 (10.5) | 5 (4.9) | 3 (7.3) |
ORR | ||||
ORR (CR + PR) | 6 (22.2) | 0 | 12 (11.8) | 0 |
DCR | ||||
DCR (CR + PR + SD) | 15 (55.6) | 4 (21.1) | 43 (42.2) | 10 (24.4) |