Table 4.

Multivariate Cox regression models for death.

Parameter/Category	Adjusted Multivariate Analysis‡
	HR	95% CI	p
Gender
Female	1†
Male	1.121	0.898-1.398	0.314
Age
≤60	1†
>60	1.192	0.961-1.478	0.109
Area of enrollment in Italy3
Center/South	1†
North	0.981	0.778-1.238	0.873
Year BRAF executed4
<2013	1†
≥2013	1.06	0.837-1.355	0.609
LDH
Normal	1.0†
Abnormal	1.95	1.24-3.01	0.004
Unknown	0.97	0.95-1.53	0.09
Target therapy
No Target and No Immuno therapy	1.0†
BRAF	1.14	0.85-1.53	0.4
BRAFI+MEKI	0.623	0.42-0.94	0.02
Immunotherapy
No Immuno and No Target therapy	1.0†
ANTI-PD-1 (Nivolumab/Pebrolizumab)	0.25	0.147-0.43	<0.0001
ANTI-CTLA4 (Ipilimumab)	0.47	0.33-0.67	<0.0001
ANTI-PD-1+ ANTI-CTLA4	0.26	0.15-0.47	<0.0001
Treatment Sequence
Immuno 1st and Target 2nd	1.0†
Target 1st and Immuno 2nd	1.64	0.65-4.12	0.3

^†Reference category; ^‡Multivariate Cox model adjusted for gender (male, female); age (≤60, >60); geographical area (North, Central-South);Year BRAF executed (≤2013, >2013); N. @ of therapies (1, 2, ≥3); Other therapies: Chemotherapy; Local and systemic therapy whenever.