Introduction
Methods
Study design
Patients
Treatment
Endpoints
Assessments
Statistical analysis
Results
Demographics and baseline characteristics
Tmab+ | Tmab− | |||
---|---|---|---|---|
Nivolumab n = 59 | Placebo n = 22 | Nivolumab n = 271 | Placebo n = 141 | |
Sex | ||||
Male | 47 (79.7) | 20 (90.9) | 182 (67.2) | 99 (70.2) |
Female | 12 (20.3) | 2 (9.1) | 89 (32.8) | 42 (29.8) |
Age (years), median (range) | 62 (23–83) | 62.5 (33–77) | 62 (20–83) | 61 (26–83) |
< 65 | 35 (59.3) | 12 (54.5) | 154 (56.8) | 83 (58.9) |
Country | ||||
Japan | 31 (52.5) | 12 (54.5) | 121 (44.6) | 62 (44.0) |
Korea | 25 (42.4) | 10 (45.5) | 121 (44.6) | 64 (45.4) |
Taiwan | 3 (5.1) | 0 | 29 (10.7) | 15 (10.6) |
ECOG performance status | ||||
0 | 19 (32.2) | 9 (40.9) | 69 (25.5) | 38 (27.0) |
1 | 40 (67.8) | 13 (59.1) | 202 (74.5) | 103 (73.0) |
Organs with metastases | ||||
< 2 | 16 (27.1) | 3 (13.6) | 71 (26.2) | 35 (24.8) |
≥ 2 | 43 (72.9) | 19 (86.4) | 200 (73.8) | 106 (75.2) |
Site of metastases | ||||
Lymph node | 49 (83.1) | 18 (81.8) | 236 (87.1) | 120 (85.1) |
Peritoneum | 5 (8.5) | 8 (36.4) | 58 (21.4) | 34 (24.1) |
Liver | 16 (27.1) | 4 (18.2) | 62 (22.9) | 24 (17.0) |
Lung | 8 (13.6) | 1 (4.5) | 10 (3.7) | 5 (3.5) |
Pleura | 1 (1.7) | 1 (4.5) | 3 (1.1) | 1 (0.7) |
Adrenal | 2 (3.4) | 1 (4.5) | 4 (1.5) | 3 (2.1) |
Bone | 1 (1.7) | 2 (9.1) | 5 (1.8) | 3 (2.1) |
Other | 6 (10.2) | 1 (4.5) | 30 (11.1) | 16 (11.3) |
Number of previous chemotherapy regimens | ||||
2 | 14 (23.7) | 2 (9.1) | 55 (20.3) | 27 (19.1) |
3 | 15 (25.4) | 7 (31.8) | 122 (45.0) | 55 (39.0) |
≥ 4 | 30 (50.8) | 13 (59.1) | 94 (34.7) | 59 (41.8) |
Previous chemotherapy | ||||
Any | 59 (100) | 22 (100) | 271 (100) | 141 (100) |
Pyrimidine analogs | 59 (100) | 22 (100) | 270 (99.6) | 141 (100) |
Platinum | 59 (100) | 22 (100) | 252 (93.0) | 135 (95.7) |
Taxane | 53 (89.8) | 19 (86.4) | 231 (85.2) | 121 (85.8) |
Irinotecan | 42 (71.2) | 18 (81.8) | 205 (75.6) | 105 (74.5) |
Ramucirumab | 9 (15.3) | 4 (18.2) | 26 (9.6) | 18 (12.8) |
Previous gastrectomy | ||||
No | 23 (39.0) | 8 (36.4) | 94 (34.7) | 43 (30.5) |
Yes | 36 (61.0) | 14 (63.6) | 177 (65.3) | 98 (69.5) |
Any post-progression therapy | ||||
Radiotherapy | 4 (6.8) | 0 | 24 (8.9) | 16 (11.3) |
Surgery | 8 (13.6) | 2 (9.1) | 59 (21.8) | 26 (18.4) |
Pharmacotherapy | 26 (44.1) | 6 (27.3) | 102 (37.6) | 51 (36.2) |
Post-progression pharmacotherapy | ||||
Fluoropyrimidine | 12 (20.3) | 4 (18.2) | 31 (11.4) | 20 (14.2) |
Taxane | 9 (15.3) | 2 (9.1) | 24 (8.9) | 14 (9.9) |
Platinum | 7 (11.9) | 3 (13.6) | 23 (8.5) | 14 (9.9) |
Irinotecan | 4 (6.8) | 1 (4.5) | 10 (3.7) | 8 (5.7) |
Ramucirumab | 10 (16.9) | 1 (4.5) | 29 (10.7) | 11 (7.8) |
Immunotherapy | 1 (1.7) | 0 | 2 (0.7) | 1 (0.7) |
Other targeted therapies | 1 (1.7) | 0 | 5 (1.8) | 5 (3.5) |
PD-L1 status (tumor cell) (%) | ||||
≥ 1 | 2 (6.5)a | 2 (13.3)b | 14 (14.1)c | 8 (17.0)d |
< 1 | 29 (93.5)a | 13 (86.7)b | 85 (85.9)c | 39 (83.0)d |
Efficacy
Tmab+ | Tmab− | |||
---|---|---|---|---|
Nivolumab n = 59 | Placebo n = 22 | Nivolumab n = 271 | Placebo n = 141 | |
BOR, n (%) | ||||
PR | 10 (16.9) | 0 | 21 (7.7) | 0 |
SD | 15 (25.4) | 7 (31.8) | 62 (22.9) | 26 (18.4) |
PD | 23 (39.0) | 10 (45.5) | 101 (37.3) | 69 (48.9) |
NE | 11 (18.6) | 5 (22.7) | 87 (32.1) | 44 (31.2) |
ORR, n (%)a | 10 (16.9) | 0 | 21 (7.7) | 0 |
DCR, n (%)a | 25 (42.4) | 7 (31.8) | 83 (30.6) | 26 (18.4) |
OS (months), median (95% CI) | 8.3 (5.3–12.9) | 3.1 (1.9–5.3) | 4.8 (4.1–6.0) | 4.2 (3.6–4.9) |
HR (95% CI)a | 0.38 (0.22–0.66) | 0.71 (0.57–0.88) | ||
P value | 0.0006 | 0.0022 | ||
P interaction, P valueb | 0.0431 | |||
PFS (months), median (95% CI) | 1.6 (1.5–4.0) | 1.5 (1.3–2.9) | 1.6 (1.5–2.4) | 1.5 (1.5–1.5) |
HR (95% CI)c | 0.49 (0.29–0.85) | 0.64 (0.51–0.80) | ||
P value | 0.0111 | 0.0001 | ||
P interaction, P valueb | 0.3046 | |||
DOR (months), median (range) | 8.6 (4.3–13.1) | – | 9.5 (2.8–22.9) | – |
TTR (months), median (range) | 3.0 (1.4–7.0) | – | 1.6 (1.4–6.2) | – |
Safety
Tmab+ | Tmab− | |||
---|---|---|---|---|
Nivolumab n = 59 | Placebo n = 22 | Nivolumab n = 271 | Placebo n = 139 | |
Common treatment-related AEsa | ||||
Pruritus | 9 (15.3) | 3 (13.6) | 21 (7.7) | 6 (4.3) |
Rash | 8 (13.6) | 1 (4.5) | 13 (4.8) | 4 (2.9) |
Diarrhea | 4 (6.8) | 0 | 19 (7.0) | 3 (2.2) |
Malaise | 3 (5.1) | 0 | 10 (3.7) | 6 (4.3) |
Nausea | 3 (5.1) | 0 | 12 (4.4) | 4 (2.9) |
ALT increased | 1 (1.7) | 0 | 7 (2.6) | 1 (0.7) |
AST increased | 1 (1.7) | 1 (4.5) | 10 (3.7) | 2 (1.4) |
Fatigue | 1 (1.7) | 2 (9.1) | 17 (6.3) | 7 (5.0) |
Hypothyroidism | 1 (1.7) | 0 | 10 (3.7) | 1 (0.7) |
Decreased appetite | 0 | 0 | 16 (5.9) | 7 (5.0) |
Pyrexia | 0 | 0 | 9 (3.3) | 3 (2.2) |
Treatment-related AEs of special interest | ||||
Maculopapular rash | 3 (5.1) | 0 | 0 | 0 |
Interstitial lung disease | 2 (3.4) | 0 | 4 (1.5) | 0 |
Hypopituitarism | 1 (1.7) | 0 | 0 | 0 |
Hypothyroidism | 1 (1.7) | 0 | 10 (3.7) | 1 (0.7) |
Acute hepatitis | 0 | 0 | 1 (0.4) | 0 |
Autoimmune thyroiditis | 0 | 0 | 1 (0.4) | 0 |
Colitis | 0 | 0 | 2 (0.7) | 0 |
Hyperthyroidism | 0 | 0 | 2 (0.7) | 0 |
Pneumonitis | 0 | 0 | 1 (0.4) | 0 |