| Reference . | Phase . | Total patient for OS . | Number of arms . | Intervention type (regimen) . | First line (%) . | Second line (%)+ . | ECOG 0-1 (%) . | Median agea (years) . | Hazard ratio (95% CI)a . | Median follow-up (months)a . |
|---|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||||
| Ascierto et al31 Checkmate 066 NCT01721772 | 3 | 418 | 2 | Nivolumab vs dacarbazine | 100 | 0 | 100 | 64 | 0.46 (0.36-0.59), P < .001. (favors nivolumab vs dacarbazine) | Min 38.4 |
| Hamid et al17 KEYNOTE-002 NCT01704287 | 2 | 540 | 3 | Pembro 2 mg/kg vs pembro 10 mg/kg vs chemotherapy | 0 | 100 | 99 | 60 (10 mg/kg) 62 (2 mg/kg) | 0.74 (0.57-0.96) P = .0106 (favors pembrolizumab 10 mg/kg vs chemotherapy) 0.86 (0.67-1.10) P = .1173 (favors pembrolizumab 2 mg/kg vs chemotherapy) | 17 |
| Hodi et al36 CheckMate 069 NCT01927419 | 2 | 142 | 2 | Nivolumab + ipilimumab vs ipilimumab | 0 | 100 | 100 | 64 | 0.74 (0.43-1.26) P = 0.26 (favors nivolumab + ipilimumab vs ipilimumab) | 24.5 |
| Hodi et al35 Checkmate 067 NCT04540705. | 3 | 945 | 3 | Nivolumab + ipilimumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 62 (ipilimumab) 60 (nivolumab) 61 (ipilimumab + nivolumab) | Not reported | Min 90 |
| Larkin et al14 Checkmate 037 NCT01721746 | 3 | 272 | 2 | Nivolumab vs. chemotherapy | 0 | 100 | 100 | 59 | 0.95 (0.73-1.24) (nivolumab vs chemotherapy) | 24 |
| Lebbe et al37 CheckMate 511 NCT02714218 | 3 and 4 | 360 | 2 | Nivolumab 1 mg/kg + ipilimumab 3 mg/kg vs nivolumab 3 mg/kg + ipilimumab 1 mg/kg | 100 | 0 | 100 | 58 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 58 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | 1.09 (0.73-1.62) (nivolumab 3 mg/kg + ipilimumab 1 mg/kg vs nivolumab 1 mg/kg + ipilimumab 3 mg/kg) | 18.6 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 18.8 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) |
| Long et al16 ECHO-301/KEYNOTE-252 NCT02752074 | 3 | 706 | 2 | Epacadostat + pembrolizumab vs pembrolizumab | 88 | 12 | 100 | 64 (epacadostat + pembrolizumab) 63 (pembrolizumab) | 1.13(0.86-1.49) (epacadostat + pembrolizumab vs pembrolizumab + placebo) | 12.4 |
| Nathan et al15 Checkmate 172 NCT02156804 | 2 | 1008 | 1 | Nivolumab | 0 | 100 | 93 | 61 | Not reported | 16.8 |
| Robert et al18 KEYNOTE 006 NCT01866319 | 3 | 834 | 3 | Pembrolizumab vs ipilimumab | 58 | 42 | 100 | 62 (combined pembrolizumab) 62 (combined ipilimumab) | 0.73 (0.61-0.88), P = 00049 (favors pembrolizumab vs ipilimumab) 0.73 (0.57-0.92), P = .0036 (favors first-line pembrolizumab vs ipilimumab) | 57.7 |
| Tawbi et al34 RELATIVITY-047 NCT03470922 | 2 and 3 | 714 | 2 | Relatlimab + nivolumab vs nivolumab | 100 | 0 | 100 | 62 (nivolumab) 63 (nivolumab + relatlimab) | 0.81 (0.64-1.01) (nivolumab + relatlimab vs nivolumab) | Min 13.2 |
| Wolchok 2022 NCT01844505 Checkmate 067 | 3 | 945 | 3 | Nivolumab + ipilimumab then nivolumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 61% <65 39% 65+ | 0.52 (0.43-0.64) (nivolumab + ipilimumab) 0.63 (0.52-0.76) (nivolumab) NA (ipilimumab) | Min 77 |
| Targeted therapy | ||||||||||
| Algazi et al27 S1320 NCT02196181 | 2 | 206 | 2 | Continuous dabrafenib + trametinib vs intermittent dabrafenib + trametinib | 70 | 30 | 100b | 61 | 1.03 (80% Cl 0.78–1.33), P = .93 (continuous vs intermittent) | 24 |
| Ascierto et al25 COLUMBUS NCT01909453 | 3 | 577 | 3 | Combo (encorafenib + binimetinib) vs encorafenib or vemurafenib | c | c | 100% | 57 (combo) 54 (encorafenib) 56 (vemurafenib) | 0.61(0.48-0.79) (favors combo vs vemurafenib) | 48.80 |
| Ascierto et al38 COBRIM NCT01689519 | 3 | 495 | 2 | Cobimetinib + vemurafenib vs vemurafenib + placebo | 100 | 0 | 100% | 55 (vemurafenib + placebo) 56 (vemurafenib + cobimetinib) | 0.8 (0.64-0.99) (favors cobimetinib + vemurafenib vs placebo + vemurafenib) | 16.6 (vemurafenib + placebo) 21.2 (vemurafenib + cobimetinib) |
| Robert et al13 COMBI-d NCT01584648 COMBI-v NCT01597908 | 3 | 563 | 2 | Dabrafenib + trametinib | 100 | 0 | 73 | 55 | Not reported | 22 |
| Reference . | Phase . | Total patient for OS . | Number of arms . | Intervention type (regimen) . | First line (%) . | Second line (%)+ . | ECOG 0-1 (%) . | Median agea (years) . | Hazard ratio (95% CI)a . | Median follow-up (months)a . |
|---|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||||
| Ascierto et al31 Checkmate 066 NCT01721772 | 3 | 418 | 2 | Nivolumab vs dacarbazine | 100 | 0 | 100 | 64 | 0.46 (0.36-0.59), P < .001. (favors nivolumab vs dacarbazine) | Min 38.4 |
| Hamid et al17 KEYNOTE-002 NCT01704287 | 2 | 540 | 3 | Pembro 2 mg/kg vs pembro 10 mg/kg vs chemotherapy | 0 | 100 | 99 | 60 (10 mg/kg) 62 (2 mg/kg) | 0.74 (0.57-0.96) P = .0106 (favors pembrolizumab 10 mg/kg vs chemotherapy) 0.86 (0.67-1.10) P = .1173 (favors pembrolizumab 2 mg/kg vs chemotherapy) | 17 |
| Hodi et al36 CheckMate 069 NCT01927419 | 2 | 142 | 2 | Nivolumab + ipilimumab vs ipilimumab | 0 | 100 | 100 | 64 | 0.74 (0.43-1.26) P = 0.26 (favors nivolumab + ipilimumab vs ipilimumab) | 24.5 |
| Hodi et al35 Checkmate 067 NCT04540705. | 3 | 945 | 3 | Nivolumab + ipilimumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 62 (ipilimumab) 60 (nivolumab) 61 (ipilimumab + nivolumab) | Not reported | Min 90 |
| Larkin et al14 Checkmate 037 NCT01721746 | 3 | 272 | 2 | Nivolumab vs. chemotherapy | 0 | 100 | 100 | 59 | 0.95 (0.73-1.24) (nivolumab vs chemotherapy) | 24 |
| Lebbe et al37 CheckMate 511 NCT02714218 | 3 and 4 | 360 | 2 | Nivolumab 1 mg/kg + ipilimumab 3 mg/kg vs nivolumab 3 mg/kg + ipilimumab 1 mg/kg | 100 | 0 | 100 | 58 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 58 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | 1.09 (0.73-1.62) (nivolumab 3 mg/kg + ipilimumab 1 mg/kg vs nivolumab 1 mg/kg + ipilimumab 3 mg/kg) | 18.6 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 18.8 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) |
| Long et al16 ECHO-301/KEYNOTE-252 NCT02752074 | 3 | 706 | 2 | Epacadostat + pembrolizumab vs pembrolizumab | 88 | 12 | 100 | 64 (epacadostat + pembrolizumab) 63 (pembrolizumab) | 1.13(0.86-1.49) (epacadostat + pembrolizumab vs pembrolizumab + placebo) | 12.4 |
| Nathan et al15 Checkmate 172 NCT02156804 | 2 | 1008 | 1 | Nivolumab | 0 | 100 | 93 | 61 | Not reported | 16.8 |
| Robert et al18 KEYNOTE 006 NCT01866319 | 3 | 834 | 3 | Pembrolizumab vs ipilimumab | 58 | 42 | 100 | 62 (combined pembrolizumab) 62 (combined ipilimumab) | 0.73 (0.61-0.88), P = 00049 (favors pembrolizumab vs ipilimumab) 0.73 (0.57-0.92), P = .0036 (favors first-line pembrolizumab vs ipilimumab) | 57.7 |
| Tawbi et al34 RELATIVITY-047 NCT03470922 | 2 and 3 | 714 | 2 | Relatlimab + nivolumab vs nivolumab | 100 | 0 | 100 | 62 (nivolumab) 63 (nivolumab + relatlimab) | 0.81 (0.64-1.01) (nivolumab + relatlimab vs nivolumab) | Min 13.2 |
| Wolchok 2022 NCT01844505 Checkmate 067 | 3 | 945 | 3 | Nivolumab + ipilimumab then nivolumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 61% <65 39% 65+ | 0.52 (0.43-0.64) (nivolumab + ipilimumab) 0.63 (0.52-0.76) (nivolumab) NA (ipilimumab) | Min 77 |
| Targeted therapy | ||||||||||
| Algazi et al27 S1320 NCT02196181 | 2 | 206 | 2 | Continuous dabrafenib + trametinib vs intermittent dabrafenib + trametinib | 70 | 30 | 100b | 61 | 1.03 (80% Cl 0.78–1.33), P = .93 (continuous vs intermittent) | 24 |
| Ascierto et al25 COLUMBUS NCT01909453 | 3 | 577 | 3 | Combo (encorafenib + binimetinib) vs encorafenib or vemurafenib | c | c | 100% | 57 (combo) 54 (encorafenib) 56 (vemurafenib) | 0.61(0.48-0.79) (favors combo vs vemurafenib) | 48.80 |
| Ascierto et al38 COBRIM NCT01689519 | 3 | 495 | 2 | Cobimetinib + vemurafenib vs vemurafenib + placebo | 100 | 0 | 100% | 55 (vemurafenib + placebo) 56 (vemurafenib + cobimetinib) | 0.8 (0.64-0.99) (favors cobimetinib + vemurafenib vs placebo + vemurafenib) | 16.6 (vemurafenib + placebo) 21.2 (vemurafenib + cobimetinib) |
| Robert et al13 COMBI-d NCT01584648 COMBI-v NCT01597908 | 3 | 563 | 2 | Dabrafenib + trametinib | 100 | 0 | 73 | 55 | Not reported | 22 |
aArms are labeled where more than one immunotherapy or targeted therapy arm is included. Where unlabeled, data refers to the sole immunotherapy or targeted therapy arm included in the study (eg, not chemotherapy).
bAll ECOG 0-2, further breakdown not specified by authors.
cAll patients were either untreated or progressed on first-line treatment.
| Reference . | Phase . | Total patient for OS . | Number of arms . | Intervention type (regimen) . | First line (%) . | Second line (%)+ . | ECOG 0-1 (%) . | Median agea (years) . | Hazard ratio (95% CI)a . | Median follow-up (months)a . |
|---|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||||
| Ascierto et al31 Checkmate 066 NCT01721772 | 3 | 418 | 2 | Nivolumab vs dacarbazine | 100 | 0 | 100 | 64 | 0.46 (0.36-0.59), P < .001. (favors nivolumab vs dacarbazine) | Min 38.4 |
| Hamid et al17 KEYNOTE-002 NCT01704287 | 2 | 540 | 3 | Pembro 2 mg/kg vs pembro 10 mg/kg vs chemotherapy | 0 | 100 | 99 | 60 (10 mg/kg) 62 (2 mg/kg) | 0.74 (0.57-0.96) P = .0106 (favors pembrolizumab 10 mg/kg vs chemotherapy) 0.86 (0.67-1.10) P = .1173 (favors pembrolizumab 2 mg/kg vs chemotherapy) | 17 |
| Hodi et al36 CheckMate 069 NCT01927419 | 2 | 142 | 2 | Nivolumab + ipilimumab vs ipilimumab | 0 | 100 | 100 | 64 | 0.74 (0.43-1.26) P = 0.26 (favors nivolumab + ipilimumab vs ipilimumab) | 24.5 |
| Hodi et al35 Checkmate 067 NCT04540705. | 3 | 945 | 3 | Nivolumab + ipilimumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 62 (ipilimumab) 60 (nivolumab) 61 (ipilimumab + nivolumab) | Not reported | Min 90 |
| Larkin et al14 Checkmate 037 NCT01721746 | 3 | 272 | 2 | Nivolumab vs. chemotherapy | 0 | 100 | 100 | 59 | 0.95 (0.73-1.24) (nivolumab vs chemotherapy) | 24 |
| Lebbe et al37 CheckMate 511 NCT02714218 | 3 and 4 | 360 | 2 | Nivolumab 1 mg/kg + ipilimumab 3 mg/kg vs nivolumab 3 mg/kg + ipilimumab 1 mg/kg | 100 | 0 | 100 | 58 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 58 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | 1.09 (0.73-1.62) (nivolumab 3 mg/kg + ipilimumab 1 mg/kg vs nivolumab 1 mg/kg + ipilimumab 3 mg/kg) | 18.6 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 18.8 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) |
| Long et al16 ECHO-301/KEYNOTE-252 NCT02752074 | 3 | 706 | 2 | Epacadostat + pembrolizumab vs pembrolizumab | 88 | 12 | 100 | 64 (epacadostat + pembrolizumab) 63 (pembrolizumab) | 1.13(0.86-1.49) (epacadostat + pembrolizumab vs pembrolizumab + placebo) | 12.4 |
| Nathan et al15 Checkmate 172 NCT02156804 | 2 | 1008 | 1 | Nivolumab | 0 | 100 | 93 | 61 | Not reported | 16.8 |
| Robert et al18 KEYNOTE 006 NCT01866319 | 3 | 834 | 3 | Pembrolizumab vs ipilimumab | 58 | 42 | 100 | 62 (combined pembrolizumab) 62 (combined ipilimumab) | 0.73 (0.61-0.88), P = 00049 (favors pembrolizumab vs ipilimumab) 0.73 (0.57-0.92), P = .0036 (favors first-line pembrolizumab vs ipilimumab) | 57.7 |
| Tawbi et al34 RELATIVITY-047 NCT03470922 | 2 and 3 | 714 | 2 | Relatlimab + nivolumab vs nivolumab | 100 | 0 | 100 | 62 (nivolumab) 63 (nivolumab + relatlimab) | 0.81 (0.64-1.01) (nivolumab + relatlimab vs nivolumab) | Min 13.2 |
| Wolchok 2022 NCT01844505 Checkmate 067 | 3 | 945 | 3 | Nivolumab + ipilimumab then nivolumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 61% <65 39% 65+ | 0.52 (0.43-0.64) (nivolumab + ipilimumab) 0.63 (0.52-0.76) (nivolumab) NA (ipilimumab) | Min 77 |
| Targeted therapy | ||||||||||
| Algazi et al27 S1320 NCT02196181 | 2 | 206 | 2 | Continuous dabrafenib + trametinib vs intermittent dabrafenib + trametinib | 70 | 30 | 100b | 61 | 1.03 (80% Cl 0.78–1.33), P = .93 (continuous vs intermittent) | 24 |
| Ascierto et al25 COLUMBUS NCT01909453 | 3 | 577 | 3 | Combo (encorafenib + binimetinib) vs encorafenib or vemurafenib | c | c | 100% | 57 (combo) 54 (encorafenib) 56 (vemurafenib) | 0.61(0.48-0.79) (favors combo vs vemurafenib) | 48.80 |
| Ascierto et al38 COBRIM NCT01689519 | 3 | 495 | 2 | Cobimetinib + vemurafenib vs vemurafenib + placebo | 100 | 0 | 100% | 55 (vemurafenib + placebo) 56 (vemurafenib + cobimetinib) | 0.8 (0.64-0.99) (favors cobimetinib + vemurafenib vs placebo + vemurafenib) | 16.6 (vemurafenib + placebo) 21.2 (vemurafenib + cobimetinib) |
| Robert et al13 COMBI-d NCT01584648 COMBI-v NCT01597908 | 3 | 563 | 2 | Dabrafenib + trametinib | 100 | 0 | 73 | 55 | Not reported | 22 |
| Reference . | Phase . | Total patient for OS . | Number of arms . | Intervention type (regimen) . | First line (%) . | Second line (%)+ . | ECOG 0-1 (%) . | Median agea (years) . | Hazard ratio (95% CI)a . | Median follow-up (months)a . |
|---|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy | ||||||||||
| Ascierto et al31 Checkmate 066 NCT01721772 | 3 | 418 | 2 | Nivolumab vs dacarbazine | 100 | 0 | 100 | 64 | 0.46 (0.36-0.59), P < .001. (favors nivolumab vs dacarbazine) | Min 38.4 |
| Hamid et al17 KEYNOTE-002 NCT01704287 | 2 | 540 | 3 | Pembro 2 mg/kg vs pembro 10 mg/kg vs chemotherapy | 0 | 100 | 99 | 60 (10 mg/kg) 62 (2 mg/kg) | 0.74 (0.57-0.96) P = .0106 (favors pembrolizumab 10 mg/kg vs chemotherapy) 0.86 (0.67-1.10) P = .1173 (favors pembrolizumab 2 mg/kg vs chemotherapy) | 17 |
| Hodi et al36 CheckMate 069 NCT01927419 | 2 | 142 | 2 | Nivolumab + ipilimumab vs ipilimumab | 0 | 100 | 100 | 64 | 0.74 (0.43-1.26) P = 0.26 (favors nivolumab + ipilimumab vs ipilimumab) | 24.5 |
| Hodi et al35 Checkmate 067 NCT04540705. | 3 | 945 | 3 | Nivolumab + ipilimumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 62 (ipilimumab) 60 (nivolumab) 61 (ipilimumab + nivolumab) | Not reported | Min 90 |
| Larkin et al14 Checkmate 037 NCT01721746 | 3 | 272 | 2 | Nivolumab vs. chemotherapy | 0 | 100 | 100 | 59 | 0.95 (0.73-1.24) (nivolumab vs chemotherapy) | 24 |
| Lebbe et al37 CheckMate 511 NCT02714218 | 3 and 4 | 360 | 2 | Nivolumab 1 mg/kg + ipilimumab 3 mg/kg vs nivolumab 3 mg/kg + ipilimumab 1 mg/kg | 100 | 0 | 100 | 58 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 58 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) | 1.09 (0.73-1.62) (nivolumab 3 mg/kg + ipilimumab 1 mg/kg vs nivolumab 1 mg/kg + ipilimumab 3 mg/kg) | 18.6 (nivolumab 1 mg/kg + ipilimumab 3 mg/kg) 18.8 (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) |
| Long et al16 ECHO-301/KEYNOTE-252 NCT02752074 | 3 | 706 | 2 | Epacadostat + pembrolizumab vs pembrolizumab | 88 | 12 | 100 | 64 (epacadostat + pembrolizumab) 63 (pembrolizumab) | 1.13(0.86-1.49) (epacadostat + pembrolizumab vs pembrolizumab + placebo) | 12.4 |
| Nathan et al15 Checkmate 172 NCT02156804 | 2 | 1008 | 1 | Nivolumab | 0 | 100 | 93 | 61 | Not reported | 16.8 |
| Robert et al18 KEYNOTE 006 NCT01866319 | 3 | 834 | 3 | Pembrolizumab vs ipilimumab | 58 | 42 | 100 | 62 (combined pembrolizumab) 62 (combined ipilimumab) | 0.73 (0.61-0.88), P = 00049 (favors pembrolizumab vs ipilimumab) 0.73 (0.57-0.92), P = .0036 (favors first-line pembrolizumab vs ipilimumab) | 57.7 |
| Tawbi et al34 RELATIVITY-047 NCT03470922 | 2 and 3 | 714 | 2 | Relatlimab + nivolumab vs nivolumab | 100 | 0 | 100 | 62 (nivolumab) 63 (nivolumab + relatlimab) | 0.81 (0.64-1.01) (nivolumab + relatlimab vs nivolumab) | Min 13.2 |
| Wolchok 2022 NCT01844505 Checkmate 067 | 3 | 945 | 3 | Nivolumab + ipilimumab then nivolumab vs nivolumab vs ipilimumab | 100 | 0 | 100 | 61% <65 39% 65+ | 0.52 (0.43-0.64) (nivolumab + ipilimumab) 0.63 (0.52-0.76) (nivolumab) NA (ipilimumab) | Min 77 |
| Targeted therapy | ||||||||||
| Algazi et al27 S1320 NCT02196181 | 2 | 206 | 2 | Continuous dabrafenib + trametinib vs intermittent dabrafenib + trametinib | 70 | 30 | 100b | 61 | 1.03 (80% Cl 0.78–1.33), P = .93 (continuous vs intermittent) | 24 |
| Ascierto et al25 COLUMBUS NCT01909453 | 3 | 577 | 3 | Combo (encorafenib + binimetinib) vs encorafenib or vemurafenib | c | c | 100% | 57 (combo) 54 (encorafenib) 56 (vemurafenib) | 0.61(0.48-0.79) (favors combo vs vemurafenib) | 48.80 |
| Ascierto et al38 COBRIM NCT01689519 | 3 | 495 | 2 | Cobimetinib + vemurafenib vs vemurafenib + placebo | 100 | 0 | 100% | 55 (vemurafenib + placebo) 56 (vemurafenib + cobimetinib) | 0.8 (0.64-0.99) (favors cobimetinib + vemurafenib vs placebo + vemurafenib) | 16.6 (vemurafenib + placebo) 21.2 (vemurafenib + cobimetinib) |
| Robert et al13 COMBI-d NCT01584648 COMBI-v NCT01597908 | 3 | 563 | 2 | Dabrafenib + trametinib | 100 | 0 | 73 | 55 | Not reported | 22 |
aArms are labeled where more than one immunotherapy or targeted therapy arm is included. Where unlabeled, data refers to the sole immunotherapy or targeted therapy arm included in the study (eg, not chemotherapy).
bAll ECOG 0-2, further breakdown not specified by authors.
cAll patients were either untreated or progressed on first-line treatment.
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