Table 1

Long-term survival in clinical trials with I-O agents or targeted therapies in patients with advanced/metastatic melanoma

StudyPhasePatient population*Duration of survival follow-up, monthsArm† (n), dosing scheduleMedian PFS, months
(95% CI)
Longest landmark
PFS rate
Median OS, months (95% CI)Longest landmark OS rate
Immune checkpoint inhibitors
 CheckMate 06712 IIIAny BRAF 60 (minimum)NIVO+IPI (314),
NIVO 1 mg/kg+IPI 3 mg/kg Q3W×4, then NIVO 3 mg/kg Q2W
11.5 (8.7 to 19.3)5 years: 36%NR (38.2 to NR)5 years: 52%
NIVO (316),
NIVO 3 mg/kg Q2W
6.9 (5.1 to 10.2)5 years: 29%36.9 (28.2 to 58.7)5 years: 44%
IPI (315),
IPI 3 mg/kg Q3W×4
2.9 (2.8 to 3.2)5 years: 8%19.9 (16.8 to 24.6)5 years: 26%
 CheckMate 06616 III BRAF wild-type60 (minimum)NIVO (210),
NIVO 3 mg/kg Q2W
5.1 (3.5 to 12.2)5 years: 28%37.3 (25.4 to 51.6)5 years: 39%
 KEYNOTE-0065 IIIAny BRAF
Data shown are for the treatment-naive patient subgroup
57.7 (median)PEMBRO (368),
PEMBRO 10 mg/kg Q2W/Q3W
11.6 (8.2 to 16.4)4 years:
26% (Q2W),
28% (Q3W)
38.7 (27.3 to 50.7)5 years:
41% (Q2W),
45% (Q3W)
IPI (181),
IPI 3 mg/kg Q3W×4
3.7 (2.8 to 4.3)NA17.1 (13.8 to 26.2)NA
 CA184-16944 IIIAny BRAF 43 (minimum) IPI 10 mg/kg (365), IPI 3 mg/kg

(362), Q3W×4
2.8 (2.8 to 3.0),
2.8 (2.8 to 2.8)
NA15.7 (11.6 to 17.8),
11.5 (9.9 to 13.3)
3 years: 31%,
23%
 KEYNOTE-00111 IAny BRAF
Data shown are for the treatment-naive patient subgroup
55 (median)PEMBRO (151),
PEMBRO 2 mg/kg Q3W/10 mg Q2W/10 mg Q3W
16.9 (9.3 to 35.5)5 years: 29%38.6 (27.2 to NR)5 years: 41%
 CA209-00445 IAny BRAF
No prior immune checkpoint inhibitor
43.1 (median)NIVO+IPI (94),
Dose-escalation study
NANANR (40.9 to NR)4 years: 57%
 CA209-00317 IPreviously treated, advanced melanoma (any BRAF), RCC, or NSCLC (only melanoma data shown)58.3 (minimum)NIVO (107),
Dose escalation 0.1 to 10 mg/kg Q2W
NANA20.3 (12.5 to 37.9)5 years: 34%
 IPI-pooled analysis46 II/IIIVariousApprox. 11 (median)IPI (1861),
Most patients received 3 or 10mg/kg
NANA11.4 (10.7 to 12.1)3 years: 22%
Other immunotherapy
 IL-2 pooled analysis19 VariousVarious62 (median)High-dose IL-2 (270),
600,000 or 720,000IU/kg
NANA11.4 (NA)NA
 ACT+IL-225 VariousPreviously treated, advanced melanoma62 (median)Autologous tumor-infiltrating lymphocytes+IL-2 after a lymphodepletionNANANA5 years: 29%
Combination-targeted therapy
 COMBI-d and COMBI-v15 III BRAF-mutant22 (median)DAB +TRAM (563),
DAB 150 mg twice daily+TRAM 2 mg once daily
11.1 (9.5 to 12.8)5 years: 19%25.9 (22.6 to 31.5)5 years: 34%
 COLUMBUS13 III BRAF-mutant48.8 (median)ENCO+BINI (192),
ENCO 450 mg once daily+BINI 45 mg twice daily
14.9 (11.0 to 20.2)3 years: 29%33.6 (24.4 to 39.2)3 years: 47%
VEM (191),
VEM 960 mg twice daily
7.3 (5.6 to 7.9)3 years: 14%16.9 (14.0 to 24.5)3 years: 31%
ENCO (194),
ENCO 300 mg once daily
9.6 (7.4 to 14.8)3 years: 25%23.5 (19.6 to 33.6)3 years: 41%
 coBRIM14 III BRAF-mutantNACOBI+VEM (247),
COBI 60 mg once daily+VEM 960 mg twice daily
12.6 (9.5 to 14.8)5 years: 14%22.5 (20.3 to 28.8)5 years: 31%
VEM (248),
VEM 960 mg twice daily
7.2 (5.6 to 7.5)5 years: 10%17.4 (14.5 to 19.8)5 years: 26%
  • *Trials were conducted solely in treatment-naive patients unless indicated.

  • †Data for control arms are only included if ipilimumab or a targeted therapy was the comparator.

  • ‡NIVO+IPI Q3W×4 (mg/kg) in one of the following cohorts: (1) NIVO 0.3+IPI 3; (2) NIVO 1+IPI 3; (2a) NIVO 3+IPI 1; (3) NIVO 3+IPI 3; (8) NIVO 1+IPI 3. Cohorts 1 to 3 received maintenance with NIVO Q3W×4, then NIVO+IPI Q12W×8.

  • ACT, adoptive cell transfer; BINI, binimetinib; COBI, cobimetinib; DAB, dabrafenib; ENCO, encorafenib; IL-2, interleukin-2; I-O, immuno-oncology; IPI, ipilimumab; NA, not available; NIVO, nivolumab; NR, not reached; NSCLC, non-small cell lung cancer; OS, overall survival; PEMBRO, pembrolizumab; PFS, progression-free survival; Q2W, every 2 weeks; Q3W, every 3 weeks; RCC, renal cell carcinoma; TRAM, trametinib; VEM, vemurafenib.