Metastatic melanoma (MM) is a pathological entity with a very poor prognosis that had a low response rate to systemic treatments. In fact, the aggressiveness of melanoma is different depending on whether it debuts directly as metastatic disease or if what occurs is a relapse after a first diagnosis at an early stage, although the biological determinants are largely unknown. Another key aspect in the clinical management of metastatic melanoma at first diagnosis strives in the different prognosis of melanoma of unknown primary (MUP) compared to melanoma of known primary (MPK).
Clinical Trial | CHECKMATE-066 [39,40,41][29][30][31] | KEYNOTE-006 [42,43][32][33] | CHECKMATE-067 [44,45][34][35] | ||||
---|---|---|---|---|---|---|---|
All patients (n%) | 78 (9.6) | 810 (100) | 1191 (26.7) | ||||
Experimental Drug | Nivo | 4459 | |||||
Pem | Nivo-Ipi | Stage | Stage IV | Stage 0-IV | Stage IV | III-IV/Recurrence | |
Control Drug | DTIC | Mean age (years) | 60.69 | 58.74 | 66 | 64.4 | |
Ipi | Ipi/Nivo | ||||||
Stage at randomization a,b (%) | Sex [n (%)] | ||||||
III | NR | ||||||
3.1 | Men | 45 (9.3) | 485 (59.9) | - | |||
IV (M1c) | 61% M1c | - | |||||
96.9 (66.2) | (58.9) | Women | 33 (10.2) | 325(40.1) | - | ||
Stage IV at first diagnosis a,b | NR | - | |||||
c | NR | NR | ECOG (%) | ||||
mPFS a | 5.1 | 8.4 | 11.5 | 0–1 | |||
mOS | 665 (55.8) | 2619 (58.7) | |||||
a | 37.3 | 31.1 | 60.0 | 2 | 96 (8.1) | 248 (5.5) | |
mOS by stage a,b: III M1a M1b M1c |
NR | NR | NR | 3–4 | 44 (3.7) | 91 (2.0) | |
MUP patients | Mean time to recurrence (years) | 3.84 ± 5.19 | 4.94 ± 6.69 | ||||
Included | |||||||
Yes | Yes | Yes | Mutation type [n (%)] | ||||
Outcomes | NR | NR | BRAF | 11 (21.6) | 51 (6.3) | 444 (37.3) | 1314 (42) |
CKIT | 1 (16.7) | 6 (0.7) | - | - | |||
NRAS | 0 | 1 (0.1) | - | - | |||
MEK | 0 | 0 | - | - | |||
GNAO | 0 | 0 | - | - | |||
GNA11 | 0 | 0 | - | - | |||
Metastatic [n (%)] | |||||||
Yes | 11 (21.6) | 354 (44.0) | |||||
No | 1 (16.7) | 454 (56.1) | |||||
Resectable [n (%)] | |||||||
Yes | 0 | 704 (86.9) | |||||
No | 78 (73.6) | 106 (13.1) | |||||
NR | Developed metastatic during course of disease | ||||||
No | 78 (100) | 454 (56.0) | |||||
Yes | 0 | 346 (42.7) | |||||
Median Overall Survival [months (95% CI)] | |||||||
Initially stage 0–II | 111.3 | ||||||
Initially stage III | (95.6–131) | ||||||
Initially stage IV | 76.3 (59.3–93.3) | ||||||
59.9 (38.2–81.7) | |||||||
First Line Treatment (%) | |||||||
Immunotherapy | 665 (73.1) | 1652 (73.5) | |||||
BRAF inhibitor | 186 (20.4) | 393 (17.5) | |||||
Clinical trial | 28 (3.1) | 106 (4.7) | |||||
Chemotherapy | 19 (2.1) | 51 (2.3) | |||||
Interferon | 5 (0.5) | 14 (0.6) | |||||
IL-2 | 1 (0.1) | 4 (0.2) |