Table 1.
Patient characteristics at start of the first PD-1-based immune checkpoint inhibition (index therapy).
| Total patient cohort |
Primary tumor |
Lymph node metastasis |
Skin/Subcutaneous metastasis |
Organ metastasis |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | N (%) | N all (%) | N PD-L1<5% (%) | N PD-L1≥5% (%) | N all (%) | N PD-L1<5% (%) | N PD-L1≥5% (%) | N all (%) | N PD-L1<5% (%) | N PD-L1≥5% (%) | N all (%) | N PD-L1<5% (%) | N PD-L1≥5% (%) |
| Total | 448 (100%) | 95 (100%) | 60 (63.2%) | 35 (36.8%) | 115 (100%) | 57 (49.6%) | 58 (50.4%) | 153 (100%) | 101 (66.0%) | 52 (34.0%) | 85 (100%) | 51 (60.0%) | 34 (40.0%) |
| Mean age (range), years | 65.2 (17.6–93.4) | 65.4 (19.9–89.8) | 64.9 (25.6–89.8) | 66.2 (19.9–89.6) | 65.9 (17.6–85.2) | 66.1 (17.6–85.2) | 65.7 (31.0–85.2) | 65.3 (27.4–91.2) | 66.4 (27.4–91.2) | 68.5 (28.3–88.5) | 61.9 (26.4–93.4) | 62.0 (26.4–93.4) | 61.9 (39.3–81.0) |
| Sex | |||||||||||||
| Female | 279 (62.2%) | 66 (69.5%) | 37 (61.7%) | 29 (82.9%) | 72 (62.6%) | 36 (63.2%) | 36 (62.1%) | 92 (60.1%) | 61 (60.4%) | 31 (59.6%) | 36 (42.4) | 25 (49.0%) | 11 (32.4%) |
| Male | 169 (37.8%) | 29 (30.5%) | 23 (38.3%) | 6 (17.1%) | 43 (37.4%) | 21 (36.8%) | 22 (37.9%) | 61 (39.9%) | 40 (39.6%) | 21 (40.4%) | 49 (57.6%) | 26 (50.1%) | 23 (67.4%) |
| Localisation of primary | |||||||||||||
| Skin | 372 (83.0%) | 79 (83.2%) | 48 (80.0%) | 31 (88.6%) | 97 (84.3%) | 48 (84.2%) | 49 (84.5%) | 141 (92.2%) | 92 (91.1%) | 49 (94.2%) | 55 (64.7) | 31 (60.8%) | 24 (70.6%) |
| Mucosa | 37 (8.3%) | 16 (16.8%) | 12 (20.0%) | 4 (11.4%) | 6 (5.2%) | 3 (5.3%) | 3 (5.2%) | 4 (26.1%) | 1 (1.0%) | 3 (5.8%) | 14 (16.5%) | 9 (17.6%) | 5 (14.7%) |
| Occult (unknown primary) | 39 (5.8%) | 0 (0%) | 0 (0%) | 0 (0%) | 12 (10.4%) | 6 (10.5%) | 6 (10.3%) | 8 (5.2%) | 8 (7.9%) | 0 (0.0%) | 16 (18.8%) | 11 (21.6%) | 5 (14.7%) |
| BRAF V600 mutation (tumor) | |||||||||||||
| Yes | 134 (29.9%) | 30 (31.6%) | 20 (33.3%) | 10 (28.6%) | 33 (28.7%) | 18 (31.6%) | 15 (25.8%) | 37 (24.2%) | 23 (22.8%) | 14 (26.9%) | 38 (44.7%) | 19 (37.3%) | 19 (55.9%) |
| No | 314 (70.1%) | 65 (68.4%) | 40 (66.7%) | 25 (71.4%) | 82 (71.3%) | 39 (68.4%) | 43 (74.1%) | 116 (75.8%) | 78 (77.2%) | 38 (73.1%) | 47 (55.3%) | 32 (62.7%) | 15 (44.1%) |
| AJCC stage and M category | |||||||||||||
| III, IV M1a/b | 262 (58.5%) | 49 (51.6%) | 35 (58.3%) | 14 (40.0%) | 76 (66.1%) | 42 (73.7%) | 34 (58.6%) | 109 (71.2%) | 72 (71.3%) | 37 (71.1%) | 28 (32.9%) | 17 (33.3%) | 11 |
| IV M1c/d | 174 (38.8%) | 34 (35.8%) | 19 (31.7%) | 15 (42.9%) | 39 (33.9%) | 15 (26.3%) | 24 (41.4%) | 44 (28.8%) | 29 (28.7%) | 15 (28.9%) | 57 (67.1%) | 34 (66.7%) | 23 |
| Unknown | 12 (2.7%) | 12 (12.6%) | 6 (10%) | 6 (17.1%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Number of organs involved in metastasis | |||||||||||||
| ≤2 | 329 (73.4%) | 65 (68.4%) | 44 (73.3%) | 21 (60.0%) | 86 (74.8%) | 45 (78.9%) | 41 (70.7%) | 118 (77.1%) | 76 (75.2%) | 42 (80.8%) | 60 (70.6%) | 37 (72.5%) | 23 (67.4%) |
| ≥3 | 102 (22.8%) | 13 (13.7%) | 7 (16.7%) | 6 (17.1%) | 29 (25.2%) | 12 (21.1%) | 17 (29.3%) | 35 (22.9%) | 25 (24.8%) | 10 (19.2%) | 25 (29.4%) | 14 (27.5%) | 11 (32.4%) |
| Unknown | 17 (3.8%) | 17 (17.9%) | 9 (15.0%) | 8 (22.9%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| LDH (serum) | |||||||||||||
| Normal (≤ULN) | 190 (42.4%) | 39 (41.1%) | 27 (45.0%) | 12 (34.3%) | 53 (46.1%) | 24 (42.1%) | 29 (50.0%) | 66 (43.1%) | 47 (46.5%) | 19 (36.5%) | 32 (37.6%) | 17 (33.3%) | 15 (44.1%) |
| Elevated (>ULN) | 156 (34.8%) | 25 (26.3%) | 16 (26.7%) | 9 (25.7%) | 37 (32.2%) | 19 (33.3%) | 18 (31.0%) | 61 (39.9%) | 40 (39.6%) | 21 (40.4%) | 33 (38.9%) | 23 (29.4%) | 10 (29.4%) |
| Unknown | 102 (22.8%) | 31 (32.6%) | 17 (28.3%) | 14 (40.0%) | 25 (21.7%) | 14 (24.6%) | 11 (19.0%) | 26 (17.0%) | 14 (13.9%) | 12 (23.1%9 | 20 (23.5%) | 11 (26.5%) | 9 (26.5%) |
| ECOG overall performance status | |||||||||||||
| 0 | 280 (62.5%) | 67 (70.5%) | 45 (75.0%) | 22 (62.9%) | 67 (58.3%) | 35 (61.4%) | 32 (55.2%) | 98 (64.1%) | 64 (63.4%) | 34 (65.4%) | 49 (57.6%) | 28 (54.9%) | 21 (61.8%) |
| ≥1 | 82 (18.3%) | 19 (20.0%) | 11 (18.3%) | 8 (22.9%) | 17 (14.8%) | 8 (14.0%) | 9 (15.5%) | 31 (20.3%) | 20 (19.8%) | 11 (21.2%) | 15 (17.6%) | 10 (19.6%) | 5 (14.7%) |
| Unknown | 86 (19.2%) | 9 (9.5%) | 4 (6.7%) | 5 (14.3%) | 31 (26.9%) | 14 (24.6%) | 17 (29.3%) | 24 (15.7%) | 17 (16.8%) | 7 (13.5%) | 21 (24.7%) | 13 (25.5%) | 8 (23.5%) |
| Non-adjuvant pre-treatment | |||||||||||||
| Yes | 110 (24.5%) | 27 (28.4%) | 23 (38.3%) | 4 (11.4%) | 26 (22.6%) | 11 (19.3%) | 15 (25.9%) | 37 (24.2%) | 23 (22.8%) | 14 (26.9%) | 35 (68.6%) | 22 (43.1%) | 13 (38.2%) |
| No | 304 (67.9%) | 60 (63.2%) | 32 (53.3%) | 28 (80%) | 84 (73.0%) | 44 (77.2%) | 40 (69.0%) | 105 (68.6%) | 70 (69.3%) | 35 (67.3%) | 37 (72.5%) | 24 (47.1%) | 13 (38.2%) |
| Unknown | 34 (7.6%) | 8 (8.4%) | 5 (8.3%) | 3 (8.6%) | 5 (4.4%) | 2 (3.5%) | 3 (5.1%) | 11 (7.2%) | 8 (7.9%) | 3 (5.7%) | 13 (25.4%) | 5 (9.8%) | 8 (23.6%) |
| Type of ICI therapy | |||||||||||||
| PD-1 | 314 (70.1%) | 62 (65.3%) | 35 (58.3%) | 27 (77.1%) | 94 (81.7%) | 48 (84.2%) | 46 (79.3%) | 113 (73.9%) | 72 (71.3%) | 41 (78.8%) | 33 (38.8%) | 24 (47.1%) | 19 (55.9%) |
| PD-1 plus CTLA-4 | 134 (29.9%) | 33 (34.7%) | 25 (41.7%) | 8 (22.9%) | 21 (18.3%) | 9 (15.8%) | 12 (20.7%) | 40 (26.1%) | 29 (28.7%) | 11 (21.2%) | 52 (61.2%) | 27 (52.9%) | 15 (44.1%) |
| Therapy Outcome | |||||||||||||
| Total | 442 (100%) | 95 (100%) | 60 (100%) | 35 (100%) | 112 (100%) | 56 (100%) | 56 (100%) | 150 (100%) | 100 (100%) | 50 (100%) | 85 (100%) | 51 (60.0%) | 34 (40.0%) |
| CR | 45 (10.2%) | 9 (9.5%) | 5 (8.3%) | 4 (11.4%) | 10 (8.9%) | 4 (7.1%) | 6 (10.7%) | 18 (12.0%) | 10 (10.0%) | 8 (16.0) | 8 (9.4%) | 4 (7.8%) | 4 (11.8%) |
| PR | 74 (16.7%) | 13 (13.7%) | 6 (10.0%) | 7 (20.0%) | 20 (17.8%) | 5 (8.9%) | 15 (26.7%) | 27 (18.0%) | 17 (17.0%) | 10 (20.0) | 14 (16.5%) | 6 (11.8%) | 8 (23.5%) |
| SD | 127 (28.7%) | 33 (34.7%) | 25 (41.7%) | 8 (22.9%) | 36 (32.1%) | 16 (28.6%) | 20 (35.7%) | 37 (24.7%) | 23 (23.0%) | 14 (28.0%) | 21 (24.7%) | 13 (25.5%) | 8 (23.5%) |
| PD | 196 (44.3%) | 40 (42.1%) | 24 (40.0%) | 16 (45.7%) | 46 (41.1) | 31 (54.4%) | 15 (26.7%) | 68 (45.3%) | 50 (50.0%) | 18 (36.0%) | 42 (49.1%) | 28 (54.9%) | 14 (41.2%) |
| ORR | |||||||||||||
| CR/PR | 119 (26.9%) | 22 (23.2%) | 11 (18.3%) | 11 (31.4%) | 30 (26.7%) | 9 (16.1%) | 21 (37.5%) | 45 (30.0%) | 27 (27.0%) | 18 (36.0%) | 22 (25.9% | 10 (19.6%) | 12 (35.3%) |
| SD/PD | 323 (73.1%) | 73 (76.8%) | 49 (81.7%) | 24 (68.6%) | 82 (73.3%) | 47 (83.9%) | 35 (62.5%) | 105 (70.0%) | 73 (73.0%) | 32 (64.0%) | 63 (74.1%) | 41 (80.4%) | 22 (64.7%) |
| DCR | |||||||||||||
| CR/PR/SD | 246 (55.6%) | 55 (57.9%) | 36 (60%) | 19 (54.3%) | 66 (58.9%) | 25 (44.6%) | 41 (73.2%) | 82 (54.7%) | 50 (50.0%) | 32 (64.0%) | 43 (50.6%) | 23 (45.1%) | 20 (58.8%) |
| PD | 196 (44.4%) | 40 (42.1%) | 24 (40.0%) | 16 (45.7%) | 46 (41.1) | 31 (55.3%) | 15 (26.8%) | 68 (45.3%) | 50 (50.0%) | 18 (36.0%) | 42 (49.1%) | 28 (54.9%) | 14 (41.2%) |
| Median PFS in months (95% CI) | 5.0 (3.5–6.6) | 5.8 (0.0–12.7) | 3.5 (1.3–5.6) | 22.0 (11.9–32.2) | 6.0 (2.5–9.5) | 7.5 (1.4–13.7) | 3.5 (2.0–4.9) | 6.3 (0.0–23.5) | |||||
| HR (95% CI) | 0.757 (0.467–1.226) | 0.490 (0.310–0.775) | 0.825 (0.555–1.226) | 0.614 (0.368–1.023) | |||||||||
| Median OS in months (95% CI) | 15.5 (9.4–21.6) | Not reached | 16.6 (9.4–23.8) | 68.9 (29.8–107.9) | 28.7 (11.5–45.8) | 31.1 (15.6–46.6) | 13.3 (4.6–21.9) | 31.5 (17.2–45.8) | |||||
| HR (95% CI) | 0.528 (0.305–0.913) | 0.519 (0.307–0.880) | 1.083 (0.698–1.681) | 0.643 (0.380–1.085) | |||||||||
Patient characteristics at start of the first non-adjuvant PD-1-based immune checkpoint inhibition (ICI) therapy of the total patient cohort and of the subgroups of patients with PD-L1 assessment in primary tumors, lymph node metastases, and skin/subcutaneous metastases. Statistical analysis of total subgroups with.
∗One-way ANOVA and ∗∗chi-square test.
AJCCv8 was used for disease classification. LDH, lactate dehydrogenase; ULN, upper limit of normal.