All patients n=450 (100%) | CTLA-4+PD-1 n=175 (100%) | PD-1 n=161 (100%) | BRAF+MEK n=114 (100%) | |
Age | ||||
≤65 years >65 years | 274 (54.9) 203 (45.1) | 102 (58.3) 73 (41.7) | 73 (45.3) 88 (54.7) | 72 (63.2) 42 (36.8) |
Gender | ||||
Male Female | 285 (63.3) 165 (36.7) | 109 (62.3) 66 (37.7) | 96 (59.6) 65 (40.4) | 80 (70.2) 34 (29.8) |
Site of primary | ||||
Cutaneous Mucosal Uveal Unspecified or unknown | 357 (79.3) 5 (1.1) 4 (0.9) 84 (18.6) | 139 (79.4) 2 (1.1) 1 (0.6) 33 (18.9) | 127 (78.9) 3 (1.9) 3 (1.9) 28 (17.4) | 91 (79.8) 0 (0.0) 0 (0.0) 23 (20.2) |
BRAF status | ||||
V600 wildtype V600E/K mutation Unknown | 191 (42.4) 219 (48.7) 40 (8.9) | 85 (48.6) 63 (36.0) 27 (15.4) | 106 (65.8) 42 (26.1) 1 (8.1) | 0 (0.0) 114 (100.0) 0 (0.0) |
Previous adjuvant therapy stage III | ||||
Yes No | 78 (17.3) 372 (82.7) | 30 (17.1) 145 (82.9) | 32 (19.9) 129 (80.1) | 16 (14.0) 98 (86.0) |
Previous adjuvant therapy stage IV | ||||
Yes No | 20 (4.4) 430 (95.6) | 6 (3.4) 169 (96.6) | 8 (5.0) 153 (95.0) | 6 (5.3) 108 (94.7) |
ECOG performance status | ||||
0 1 ≥2 Unknown | 164 (36.4) 84 (18.7) 30 (6.7) 172 (38.2) | 83 (47.4) 26 (14.9) 8 (4.6) 58 (33.1) | 51 (31.7) 38 (23.6) 9 (5.6) 63 (39.1) | 30 (26.3) 20 (17.5) 13 (11.4) 51 (44.7) |
Serum LDH | ||||
Normal (≤ULN) Elevated (>ULN) >10× ULN Unknown | 146 (32.4) 199 (44.2) 43 (9.6) 105 (23.3) | 57 (32.6) 73 (41.7) 17 (9.7) 45 (25.7) | 62 (38.5) 72 (44.7) 12 (7.5) 27 (16.8) | 27 (23.7) 54 (47.4) 14 (12.3) 33 (28.9) |
Extracranial affected organ sites | ||||
0 1–2 ≥3 | 81 (18.0) 218 (48.4) 151 (33.6) | 31 (17.7) 89 (50.9) 55 (31.4) | 32 (19.9) 77 (47.8) 52 (32.3) | 18 (15.8) 52 (45.6) 44 (38.6) |
Number of brain metastases | ||||
1 2–4 ≥5 Unknown | 114 (25.3) 111 (24.7) 157 (34.9) 68 (15.1) | 47 (26.9) 42 (24.0) 56 (32.0) 30 (17.1) | 40 (24.8) 41 (25.5) 61 (37.9) 19 (11.8) | 27 (23.7) 28 (24.6) 40 (35.1) 19 (16.7) |
Maximal size of brain metastases | ||||
≤1 cm >1 cm Unknown | 127 (28.2) 136 (30.2) 187 (41.6) | 51 (29.1) 47 (26.9) 77 (44.0) | 46 (28.6) 47 (29.2) 68 (42.2) | 30 (26.3) 42 (36.8) 42 (36.8) |
Maximal size of brain metastases | ||||
No Yes Unknown | 291 (64.7) 118 (26.2) 41 (9.1) | 118 (67.4) 42 (24.0) 15 (8.6) | 106 (65.8) 37 (23.0) 18 (11.2) | 67 (58.8) 39 (34.2) 8 (7.0) |
Dexamethasone intake at therapy start | ||||
No Yes Unknown | 314 (69.8) 95 (21.1) 41 (9.1) | 127 (72.6) 35 (20.0) 13 (7.4) | 114 (70.8) 28 (17.4) 19 (11.8) | 73 (64.0) 32 (28.1) 9 (7.9) |
Radiotherapy of brain metastases | ||||
None Stereotactic Conventional Stereotactic and conventional | 147 (32.7) 137 (30.4) 135 (30.0) 31 (6.9) | 61 (34.9) 46 (26.3) 56 (32.0) 12 (6.9) | 47 (29.2) 52 (32.2) 50 (31.1) 12 (7.5) | 39 (34.2) 39 (34.2) 29 (25.4) 7 (6.1) |
Surgery of brain metastases | ||||
No Yes | 340 (75.6) 110 (24.4) | 134 (76.6) 41 (23.4) | 122 (75.8) 39 (24.2) | 84 (73.7) 30 (26.3) |
Best overall response | ||||
CR PR SD PD Unknown | 42 (9.3) 120 (26.7) 62 (13.8) 189 (42.0) 36 (8.0) | 12 (6.9) 42 (24.0) 20 (11.4) 82 (46.9) 19 (10.9) | 24 (14.9) 38 (23.6) 23 (14.3) 66 (41.0) 10 (6.2) | 6 (5.3) 40 (35.1) 19 (16.7) 41 (36.0) 8 (7.0) |
Best extracranial response | ||||
NED CR PR SD PD Unknown | 35 (7.8) 51 (11.3) 105 (23.3) 75 (16.7) 106 (23.6) 78 (18.3) | 12 (6.9) 14 (8.0) 37 (21.1) 28 (16.0) 47 (26.9) 37 (21.1) | 15 (9.3) 25 (15.5) 33 (20.5) 20 (12.4) 39 (24.2) 29 (18.0) | 8 (7.0) 12 (10.5) 35 (30.7) 27 (23.7) 20 (17.5) 12 (10.5) |
Best intracranial response | ||||
CR PR SD PD Unknown | 70 (15.6) 104 (23.1) 60 (13.3) 135 (30.0) 81 (18.0) | 24 (13.8) 35 (20.0) 24 (13.7) 58 (33.1) 34 (19.4) | 35 (22.7) 31 (19.3) 17 (10.6) 46 (28.6) 32 (19.9) | 11 (9.7) 38 (33.3) 19 (16.7) 31 (27.2) 15 (13.2) |
Therapy end reason | ||||
Planned stop Toxicity Disease progression Patient wish Other Ongoing Lost to follow-up | 7 (1.6) 81 (18.0) 238 (52.9) 16 (3.6) 36 (8.0) 65 (14.4) 7 (1.5) | 1 (0.6) 54 (30.9) 69 (39.4) 3 (1.7) 12 (6.9) 33 (18.9) 3 (1.7) | 6 (3.7) 19 (11.8) 86 (53.4) 9 (5.6) 17 (10.6) 20 (12.4) 4 (2.5) | 0 (0.0) 7 (6.1) 85 (74.6) 5 (4.4) 6 (5.3) 11 (9.6) 0 (0.0) |
Progression | ||||
No Yes | 120 (26.7) 330 (73.3) | 63 (36.0) 112 (64.0) | 40 (24.8) 121 (75.2) | 17 (14.9) 97 (85.1) |
Death | ||||
No Yes | 236 (52.4) 214 (47.6) | 112 (64.0) 63 (36.0) | 82 (50.9) 79 (49.1) | 42 (36.8) 72 (63.0) |
Progression-free survival | ||||
Median in months (95% CI) | 4.7 (3.9 to 5.6) | 3.9 (2.3 to 5.5) | 5.4 (2.0 to 8.8) | 5.0 (4.3 to 5.8) |
Overall survival | ||||
Median in months (95% CI) | 21.5 (16.9 to 26.0) | Not reached | 26.6 (12.0 to 40.5) | 16.5 (8.9 to 24.1) |
CR, complete response; LDH, lactate dehydrogenase; NED, no evidence of disease; PD, progressive disease; PR, partial response; SD, stable disease; ULN, upper level of norm.