Table 1.
Univariate analyses of characteristics of the 70 metastatic melanoma patients given anti-PD-1 immunotherapy as a function of outcome measures
| Characteristic | Valuea | 6-month ORR (%) | Overall survival (%) | PFS (median, months) | |
|---|---|---|---|---|---|
| 6 months | 12 months | ||||
| Clinical | |||||
| Gender | NS | ||||
| Male | 58.6 (41) | 31.7 | |||
| Female | 41.4 (29) | 24.1 | |||
| Age (years) | NS | ||||
| <60 | 38.6 (27) | 37 | |||
| >60 | 61.4 (43) | 23.2 | |||
| Lactate dehydrogenase | NS | NS | NS | ||
| <1 Normal | 37.5 (18/48) | 38.8 | 76.5 | 70.6 | 11.7 |
| >1 Normal | 62.5 (30/48) | 20 | 70 | 56.7 | 5 |
| Metastases | |||||
| Chronology | P=0.04 | P=0.002 | P=0.049 | ||
| Synchronous | 27.1 (19) | 10.5 | 36.8 | 31.6 | 3 |
| Metachronous | 72.9 (51) | 35.3 | 82 | 65.14 | 10.3 |
| Months to onset, median (range) | 24 (1.1–219) | NS | |||
| Previous treatments | NS | NS | NS | ||
| None | 25.7 (18) | 33.3 | 77.78 | 60.6 | 8.9 |
| 1 treatment | 41.4 (29) | 20.7 | 68.14 | 53 | 5 |
| >1 treatment | 32.9 (23) | 34.8 | 65.22 | 56 | 5.6 |
| Anti-PD-1 immunotherapy | |||||
| Treatment line, median (range) | 2 (1–8) | NS | |||
| Molecule | NS | ||||
| Pembrolizumab | 72.9 (51) | 27.45 | |||
| Nivolumab | 27.1 (19) | 31.6 | |||
| Days of treatment, median (range) | 148.5 (7–745) | P≤0.0001 | |||
| Number of cycles, median (range) | 10.5 (1–39) | P≤0.0001 | |||
| Immune adverse events | |||||
| Acute | 21.4 (15) | NS | |||
| Chronic | 50 (31/62) | NS | |||
| Follow-up (all patients) | |||||
| 6-month ORR, % (n) | 28.6 (20) | ||||
| Median follow-up (months) | 19.3 | ||||
| 12-month OS (%) | 56 | ||||
| Median OS (months) | 15.9 | ||||
| Median PFS (months) | 5.75 | ||||
| Alive at the end of the follow-up, % (n) | 50 (35) | ||||
| Morphological and molecular | |||||
| Primary tumour | |||||
| pT | NS | NS | NS | ||
| T1/T2 | 32.3 (20/62) | 20 | 60 | 40 | 3.3 |
| T3/T4 | 67.7 (42/62) | 31 | 76 | 63.1 | 5.7 |
| pN | NS | NS | NS | ||
| N0/N1 | 42.4 (25/59) | 36 | 67 | 57.5 | 5.7 |
| N2/N3 | 57.6 (34/59) | 23.5 | 73.5 | 61.8 | 5.6 |
| pM | NS | NS | NS | ||
| M0 | 34.3 (24) | 33.3 | 70.8 | 51.5 | 5.7 |
| M1 (a, b or c) | 65.7 (46) | 26 | 69.1 | 58 | 5.6 |
| TILs | NS | ||||
| Yes | 75 (36/48) | 16.7 | |||
| No | 25 (12/48) | 25 | |||
| Brisk TILs | NS | ||||
| Yes | 66.7 (24/36) | 16.7 | |||
| No | 33.3 (12/36) | 29.1 | |||
| Brisk TIL pattern | NS | ||||
| Intratumoural | 45.2 (14/31) | 21.4 | |||
| Peritumoural | 54.8 (17/31) | 35.3 | |||
| Other features | |||||
| Ulceration | 44.3 (27/61) | NS | |||
| Median (range) Breslow, mm (n=63) | 3.3 (0.2–15) | NS | |||
| PD-L1+ tumour area | P=0.02 | NS | NS | ||
| >5% | 58.3 (28/48) | 35.7 | 59.6 | 48.4 | 3.9 |
| <5% | 41.7 (20/48) | 5 | 85 | 70 | 8.4 |
| PD-L1+ at advancing edges | NS | NS | NS | ||
| >10% | 46.8 (22/47) | 31.8 | 57.75 | 43.3 | 2.8 |
| <10% | 53.2 (25/47) | 16 | 84 | 72 | 8.9 |
| PD-L1+ tumour cells | NS | NS | NS | ||
| >5% | 10.4 (5/48) | 40 | 74.1 | 40 | 3 |
| <5% | 89.6 (43/48) | 21 | 40 | 60 | 5.6 |
| CD163+ cells at advancing edges | P=0.009 | NS | P=0.04 | ||
| >10% | 68.1 (32/47) | 34.3 | 73.3 | 61.5 | 8.4 |
| <10% | 31.9 (15/47) | 0 | 71.3 | 53.3 | 2.8 |
| Metastasis | |||||
| TILs | NS | ||||
| Yes | 57.9 (22/38) | 31.8 | |||
| No | 42.1 (16/38) | 25 | |||
| Brisk TILs | NS | ||||
| Yes | 63.6 (14/22) | 28.6 | |||
| No | 36.4 (8/22) | 37.5 | |||
| Brisk TIL pattern | NS | ||||
| Intratumoural | 58.8 (10/17) | 40 | |||
| Peritumoural | 41.2 (7/17) | 14.3 | |||
| PD-L1+ tumour area | NS | NS | NS | ||
| >5% | 61.4 (43) | 30.2 | 62.8 | 51.1 | 8.9 |
| <5% | 38.6 (27) | 25.9 | 81 | 63.8 | 5 |
| PD-L1+ at advancing edges | NS | P=0.025 | NS | ||
| >10% | 46.2 (30/65) | 20 | 50 | 43.3 | 3 |
| <10% | 53.8 (35/65) | 34.3 | 85.4 | 63 | 8.4 |
| PD-L1+ tumour cells | NS | NS | NS | ||
| >5% | 21.4 (15) | 46.6 | 60 | 46.7 | 8.7 |
| <5% | 78.6 (55) | 23.6 | 72.4 | 58.7 | 5.6 |
| CD163+ cells at advancing edges | NS | NS | NS | ||
| >10% | 53.8 (35/65) | 25.7 | 64.9 | 49 | 3.9 |
| <10% | 46.2 (30/65) | 30 | 76.7 | 66.7 | 8.4 |
| Primary tumour and metastasis agreement | |||||
| PD-L1+ tumour area | 43.2 (19/44) | NS | NS | NS | |
| CD163+ advanced edges | 45.4 (20/44) | NS | NS | NS | |
| TILs (n=24) | 37.5 (9) | NS | NS | NS | |
| Mutations | |||||
| At least one | 62.9 (44) | P=0.06 | NS | P=0.059 | |
| BRAF | NS | ||||
| + | 40 (28) | 25 | |||
| – | 60 (42) | 30.9 | |||
| NRAS | P=0.019 | NS | NS | ||
| + | 22.7 (15/66) | 53.3 | 80 | 66 | 15.1 |
| – | 77.3 (51/66) | 19.6 | 68.2 | 53.4 | 3.9 |
| cKIT (n=54) | NS | ||||
| + | 1.9 (1/54) | 100 | |||
| – | 98.1 (53/54) | 26.4 | |||
ORR objective response rate, OS overall survival, PFS progression-free survival, NS non-significant: ≥0.05, PD-1 programmed death-1, PD-L1 programmed death-ligand-1, TILs tumour-infiltrating T lymphocytes.
aValues are expressed as n (%) or median (range)