Table 2.

Results of randomized phase III clinical trials in adjuvant setting for nodal-metastatic melanoma

Study	No. pts	Treatment	Primary endpoint	RFS	OS	Gr ≥3 Adverse events
Eggermont, et al. [44–46], NCT00636168 (EORTC 18071)	951	Ipilimumab (Ipi) vs placebo	RFS	HR 0.76 (95% CI 0.64–0.89); p < 0.001 Medium: Ipi 26 mo.; Placebo 17 mo	HR 0.72 (95.1% CI 0.58–0.88); p = 0.001 OS rate at 5 yr.: Ipi 65.4%; Placebo 54.5%	Ipi 54%; Placebo 26%
Tarhini, et al. [48], NCT01274338 (E1609)	1670	High-dose Ipi vs Low-dose Ipi vs High-dose IFN-α	OS; RFS	Low-dose Ipi vs High-dose IFN-α HR 0.85 (99.4% CI 0.66–1.09); p = 0.065 High-dose Ipil vs High-dose IFN-α HR 0.84 (99.4% CI 0.65–1.09); p, NS	Low-dose Ipi vs High-dose IFN-α HR 0.78 (95.6% CI 0.61–0.99); p = 0.044 High-dose Ipi vs High-dose IFN-α HR 0.88 (95.6% CI 0.69–1.12); p, NS	Low-dose Ipi 37%; High-dose Ipi 58%; High-dose IFN-α 79%
Eggermon, et al. [51, 52], EORTC 1325 (KEYNOTE-054)	1019	Pembrolizumab (Pembro) vs placebo	RFS	HR 0.57 (98.4% CI 0.43–0.74); p < 0.001 RFS rate at 12 mo.: Pembro 75%; Placebo 61%	n/a	Pembro 15%; Placebo 3%
Weber, et al. [53], NCT02388906 (CheckMate-238)	906	Nivolumab (Nivo) vs Ipilimumab	RFS	HR 0.65 (97.56% CI 0.51–0.83); p < 0.001 RFS rate at 12 mo.: Nivo 71%; Ipi 61%	n/a	Nivo 14%; Ipi 46%
Long, et al. [35, 56], NCT01682083 (COMBI-AD)	870	Dabrafenib + Trametinib (Dab + Tram) vs placebo	RFS; OS	HR 0.47 (95% CI 0.39–0.58), p < 0.001 RFS rate at 3 yr.: Dab + Tram 58%; Placebo 39%	HR 0.57 (95% CI 0.42–0.79), p = 0.0006 OS rate at 3 yr.: Dab + Tram 86%; Placebo 77%	Dab + Tram 36%; Placebo 10%
Maio, et al. [61], NCT01667419 (BRIM8)	498	Vemurafenib (Vem) vs placebo	DFS	HR 0.80 (95% CI 0.54–1.18); p = 0.26 Median (cohort 2): Vem 23 mo.; Placebo 15 mo	n/a	Vem 57%; Placebo 15%

No. Pts number of patients, OS overall Survival, RFS recurrence-free survival, DFS disease-free survival, mo months, yr years, HR hazard ratio, CI confidence interval, p p-value, n/a not available