metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
mML - NA - all population metastatic/adv melanoma (mML) mML - (neo)adjuvant (NA) mML - NA - all population
versus interferon alpha
	Ipilimumab (10 mg/kg)
	E1609 (ipi10), 2020 J Clin Oncol 2020; 38:567-575 NCT01274338	RCT	mML - NA - all population	ipilimumab 10 mg/kg	HDI high dose of interferon alpha	melanoma of cutaneous or unknown primary origin (AJCC 7th edition stage IIIB, IIIC, or IV [M1a or M1b]) who were rendered disease free surgically. No priorsystemic adjuvant therapy was permitted.	511 / 636	high	inconclusive	inconclusive 12 % decrease in deaths (OS) (PE) inconclusive 16 % decrease in RFS/DFS (PE)
	ipilimumab alone
	E1609 (ipi3), 2020 J Clin Oncol 2020; 38:567-575 NCT01274338	RCT	mML - NA - all population	ipilimumab 3 mg/kg	HDI high dose of interferon alpha	melanoma of cutaneous or unknown primary origin (AJCC 7th edition stage IIIB, IIIC, or IV [M1a or M1b]) who were rendered disease free surgically. No priorsystemic adjuvant therapy was permitted.	523 / 636	high	conclusif	demonstrated 22 % decrease in deaths (OS) (PE) inconclusive 15 % decrease in RFS/DFS (PE)
versus Ipilimumab (10 mg/kg)
	nivolumab alone
	CheckMate 238, 2017 N Engl J Med 2017;377:1824-1835 Journal of Dermatology 2019; 46:1197-. Lancet Oncol 2020 Sep 18;S1470-2045(20)30494-0. NCT02388906	RCT	mML - NA - all population	nivolumab	ipilimumab	patient, 15 years of age or older, with high-risk resected stage IIIB, IIIC, or IV melanoma as adjuvant treatment	453 / 453	low	conclusif	demonstrated 35 % decrease in RFS/DFS (PE) suggested 27 % decrease in MFS suggested 29 % decrease in RFS (extension)
versus nivolumab alone
	nivolumab plus ipilimumab
	IMMUNED (NI vs N) EXPLORATORY, 2020 Lancet 2020; 395:1558-1568 NCT02523313	RCT	mML - NA - all population	nivolumab plus ipilimumab	nivolumab	adjuvant therapy with nivolumab alone or in combination with ipilimumab compared with placebo in patients with stage IV melanoma with no evidence of disease	56 / 59	low	inconclusive	suggested 60 % decrease in RFS/DFS
versus placebo
	Ipilimumab (10 mg/kg)
	EORTC 18071, 2015 N. Engl. J. Med. 2016; 375:1845-1855 Lancet Oncol. 2017; 18:393-403 Eur. J. Cancer 2019; 119:1-10 Lancet Oncol. 2015; 16:522-30 NCT00636168	RCT	mML - NA - all population	ipilimumab	placebo	patients with completely resected high-risk stage III melanoma who had not received previous systemic therapy for melanoma	475 / 476	low	conclusif	demonstrated 28 % decrease in deaths (OS) (PE) demonstrated 25 % decrease in RFS/DFS (PE) demonstrated 24 % decrease in MFS (PE) suggested 27 % decrease in deaths (OS) (extension) more...
	nivolumab alone
	IMMUNED (N vs P ; all population), 2020 Lancet 2020; 395:1558-1568 NCT02523313	RCT	mML - NA - all population	nivolumab	placebo	adjuvant therapy with nivolumab alone or in combination with ipilimumab compared with placebo in patients with stage IV melanoma with no evidence of disease	59 / 52	low	conclusif	demonstrated 44 % decrease in RFS/DFS (PE)
	nivolumab plus ipilimumab
	IMMUNED (NI vs P ; all population), 2020 Lancet 2020; 395:1558-1568 NCT02523313	RCT	mML - NA - all population	nivolumab plus ipilimumab	placebo	adjuvant therapy with nivolumab alone or in combination with ipilimumab compared with placebo in patients with stage IV melanoma with no evidence of disease	56 / 52	low	conclusif	demonstrated 77 % decrease in RFS/DFS (PE)
	pembrolizumab alone
	KEYNOTE 054 (all population), 2018 N. Engl. J. Med. 2018; 378:1789-1801 JAMA Oncol 2020; : European Journal of Cancer 2019; 116:148-. J Clin Oncol 2020 Sep 18;JCO2002110. J Med Econ 2019 Oct;22(10):981-993. JAMA Oncol 2020; 6:519-527 Lancet Oncol 2021 Apr 12;S1470-2045(21)00065-6. Lancet Oncol 2021 Apr 12;S1470-2045(21)00081-4. NEJM Evidence NCT02362594	RCT	mML - NA - all population	pembrolizumab	placebo	patients with complete Resection of High-Risk Stage III Melanoma, stage IIIA, IIIB or IIIC melanoma with no in-transit metastases,	514 / 505	low	conclusif	demonstrated 43 % decrease in RFS/DFS (PE) suggested 47 % decrease in MFS suggested 44 % decrease in RFS (extension) suggested 41 % decrease in RFS (extension) more...
mML - NA - PDL1 positive metastatic/adv melanoma (mML) mML - (neo)adjuvant (NA) mML - NA - PDL1 positive
versus placebo
	pembrolizumab alone
	KEYNOTE 054 (PDL1>1%), 2018 N. Engl. J. Med. 2018; 378:1789-1801 JAMA Oncol 2020; : European Journal of Cancer 2019; 116:148-. J Clin Oncol 2020 Sep 18;JCO2002110. J Clin Oncol 2020 Nov 20;38(33):3925-3936. J Med Econ 2019 Oct;22(10):981-993. Lancet Oncol 2021 Apr 12;S1470-2045(21)00065-6. Lancet Oncol 2021 Apr 12;S1470-2045(21)00081-4. NCT02362594	RCT	mML - NA - PDL1 positive	pembrolizumab	placebo	patients with complete Resection of High-Risk Stage III Melanoma, stage IIIA, IIIB or IIIC melanoma with no in-transit metastases, with PDL1 positive status	428 / 425	low	conclusif	demonstrated 46 % decrease in RFS/DFS (PE) suggested 43 % decrease in RFS (extension) demonstrated 40 % decrease in DMFS (PE)
mML - L1 - all population metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - all population
versus ipilimumab alone
	nivolumab alone
	CheckMate 067 (N vs I ; all population), 2015 N Engl J Med 2017;377:1345-1356 N. Engl. J. Med. 2019; 381:1535-1546 Lancet Oncol. 2018; 19:1480-1492 N. Engl. J. Med. 2015; 373:23-34 Eur. J. Cancer 2017; 82:80-91 Qual Life Res 2019; 28:109-119 J Clin Oncol 2022; 40:127-137-. NCT01844505	RCT	mML - L1 - all population	nivolumab	ipilimumab	with previously untreated, unresectable or metastatic histologically confirmed stage III or IV melanoma.	316 / 315	low	conclusif	demonstrated 37 % decrease in deaths (OS) (PE) demonstrated 43 % decrease in progression or deaths (PFS) (PE) suggested 37 % decrease in deaths (OS) (extension) suggested 47 % decrease in PFS (extension) more...
	nivolumab plus ipilimumab
	CheckMate 067 (NI vs I ; all population), 2015 N Engl J Med 2017;377:1345-1356 N. Engl. J. Med. 2019; 381:1535-1546 Lancet Oncol. 2018; 19:1480-1492 N. Engl. J. Med. 2015; 373:23-34 Eur. J. Cancer 2017; 82:80-91 Qual Life Res 2019; 28:109-119 NCT01844505	RCT	mML - L1 - all population	nivolumab plus ipilimumab	ipilimumab	patients with previously untreated, unresectable or metastatic histologically confirmed stage III or IV melanoma.	314 / 315	low	conclusif	demonstrated 45 % decrease in deaths (OS) (PE) demonstrated 58 % decrease in progression or deaths (PFS) (PE) suggested 48 % decrease in deaths (OS) (extension) suggested 58 % decrease in PFS (extension) more...
	CheckMate 069 (all population), 2015 N Engl J Med 2015;372:2006-17 Lancet Oncol. 2016; 17:1558-1568 NCT01927419	RCT	mML - L1 - all population	nivolumab and ipilimumab	ipilimumab	unresectable, previously untreated stage III or IV melanoma with measurable disease, with BRAF Wild-Type Tumors and BRAF mutant	95 / 47	low	conclusif	demonstrated 62 % decrease in progression or deaths (PFS) (PE) suggested 64 % decrease in PFS (extension) demonstrated 14.1-fold increase in objective responses (ORR) (PE)
versus ipilimumab followed by nivolumab
	nivolumab followed by ipilimumab
	CheckMate 064, 2016 Lancet Oncol. 2016; 17:943-955 NCT01783938	RCT	mML - L1 - all population	nivolumab followed by ipilimumab	ipilimumab followed by nivolumab	unresectable stage III or stage IV melanoma, and were previously untreated or had progressed after no more than one previous systemic therapy	68 / 70	high	suggested	suggested 52 % decrease in deaths (OS)
versus nivolumab alone
	nivolumab plus ipilimumab
	CheckMate 067 (NI vs N) EXPLORATORY, 2015 N Engl J Med 2017;377:1345-1356 N. Engl. J. Med. 2019; 381:1535-1546 Lancet Oncol. 2018; 19:1480-1492 N. Engl. J. Med. 2015; 373:23-34 Eur. J. Cancer 2017; 82:80-91 Qual Life Res 2019; 28:109-119 NCT01844505	RCT	mML - L1 - all population	nivolumab plus ipilimumab	nivolumab	patients with previously untreated, unresectable or metastatic histologically confirmed stage III or IV melanoma.	314 / 316	low	inconclusive	suggested 35 % decrease in deaths (OS) suggested 21 % decrease in PFS (extension) suggested 26 % decrease in progression or deaths (PFS)
	relatlimab plus nivolumab
	RELATIVITY-047 unpublished New England Journal of Medicine NCT03470922	RCT	mML - L1 - all population	relatlimab plus nivolumab	nivolumab	patient (>= 12yr) with previously untreated, unresectable or metastatic disease melanoma	-/-	NA	suggested	suggested 25 % decrease in progression or deaths (PFS) (PE)
versus Standard of Care (SoC)
	tremelimumab
	A3671009, 2013 J. Clin. Oncol. 2013; 31:616-22 NCT00257205	RCT	mML - L1 - all population	tremelimumab	physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine)	patients with treatment-naive, unresectable stage IIic or IV melanoma	328 / 327	some concern	inconclusive	inconclusive 12 % decrease in deaths (OS) (PE) INCONCLUSIVE FOR OS
mML - L1 - BRAF mutant metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - BRAF mutant
versus ipilimumab alone
	nivolumab plus ipilimumab
	CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 N Engl J Med 2015;372:2006-17 Lancet Oncol. 2016; 17:1558-1568 NCT01927419	RCT	mML - L1 - BRAF mutant	nivolumab and ipilimumab	ipilimumab	unresectable, previously untreated stage III or IV melanoma with measurable disease, with BRAF mutant Tumors	23 / 10	low	inconclusive	no statistically significant result
versus placebo plus SoC
	atezolizumab plus SoC
	IMspire-150 (BRAF mutant), 2020 Lancet 2020; 395:1835-1844 NCT02908672	RCT	mML - L1 - BRAF mutant	atezolizumab plus cobimetinib plus vemurafenib	placebo plus cobimetinib plus vemurafenib	patients previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.	256 / 258	low	suggested	suggested 22 % decrease in progression or deaths (PFS) (PE)
mML - L1 - BRAF wild metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - BRAF wild
versus dacarbazine
	nivolumab alone
	CheckMate 066, 2015 N Engl J Med 2015;372:320-30 JAMA Oncol 2019; 5:187-194 Ann. Oncol. 2016; 27:1940-6 NCT01721772	RCT	mML - L1 - BRAF wild	nivolumab	dacarbazine	previously untreated patients who had unresectable metastatic melanoma without a BRAF mutation (stage III or IV).	210 / 208	low	conclusif	demonstrated 58 % decrease in deaths (OS) (PE) demonstrated 57 % decrease in progression or deaths (PFS) (PE) suggested 54 % decrease in deaths (OS) (extension) suggested 58 % decrease in PFS (extension) more...
versus ipilimumab alone
	nivolumab plus ipilimumab
	CheckMate 069 (BRAF wild type), 2015 N Engl J Med 2015;372:2006-17 Lancet Oncol. 2016; 17:1558-1568 NCT01927419	RCT	mML - L1 - BRAF wild	nivolumab and ipilimumab	ipilimumab	unresectable, previously untreated stage III or IV melanoma with measurable disease, with BRAF Wild-Type Tumors	72 / 37	low	conclusif	demonstrated 60 % decrease in progression or deaths (PFS) (PE) demonstrated 12.0-fold increase in objective responses (ORR) (PE)
versus pembrolizumab alone
	atezolizumab plus cometinib
	IMspire-170, 2020 Ann Oncol 2020 Dec 10;S0923-7534(20)43203-X. NCT03273153	RCT	mML - L1 - BRAF wild	cometinib plus atezolizumab	pembrolizumab	patient with confirmed locally advanced and unresectable or metastatic melanoma that was negative for BRAFV600 mutations with no prior systemic treatment for advanced melanoma.	222 / 224	some concern	inconclusive	inconclusive 15 % increase in progression or deaths (PFS) (PE)
mML - L2 - all population metastatic/adv melanoma (mML) mML - 2nd line (L2) mML - L2 - all population
versus gp100
	ipilimumab alone
	MDX010 Ipi vs gp100, 2010 N Engl J Med 2010;363:711-23 Ann. Oncol. 2013; 24:2694-8 Clin. Cancer Res. 2013; 19:2232-9 Cancer 2013; 119:1675-82 NCT00094653	RCT	mML - L2 - all population	ipilimumab	gp100	patients with previously treated metastatic melanoma and had received a previous therapeutic regimen	137 / 136	low	conclusif	demonstrated 34 % decrease in deaths (OS) (PE)
	ipilimumab plus gp100
	MDX010 Ipi plus gp100 vs gp100, 2010 N Engl J Med 2010;363:711-23 Ann. Oncol. 2013; 24:2694-8 Clin. Cancer Res. 2013; 19:2232-9 Cancer 2013; 119:1675-82 NCT00094653	RCT	mML - L2 - all population	ipilimumab plus a gp100 peptide vaccine	gp100	patients with previously treated metastatic melanoma and had received a previous therapeutic regimen	403 / 136	low	conclusif	demonstrated 32 % decrease in deaths (OS) (PE)
versus ipilimumab alone
	Ipilimumab (10 mg/kg)
	Ascierto (ipi 10 vs 3 mg/kg), 2017 Lancet Oncol. 2017; 18:611-622 NCT01515189	RCT	mML - L2 - all population	ipilimumab 10 mg	Ipilimumab 3 mg	Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors,	365 / 362	low	conclusif	demonstrated 16 % decrease in deaths (OS) (PE)
	ipilimumab plus gp100
	MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 N Engl J Med 2010;363:711-23 Ann. Oncol. 2013; 24:2694-8 Clin. Cancer Res. 2013; 19:2232-9 Cancer 2013; 119:1675-82 NCT00094653	RCT	mML - L2 - all population	ipilimumab plus gp100	Ipilimumab	patients with previously treated metastatic melanoma and had received a previous therapeutic regimen	403 / 137	low	inconclusive	statistically significant 51 % decrease in objective responses (ORR)
	pembrolizumab (10mg/kg)
	KEYNOTE-006 (3 week), 2015 Lancet 2017;390:1853-1862 N Engl J Med 2015;372:2521-32 Lancet Oncol. 2019; 20:1239-1251 Eur. J. Cancer 2018; 101:236-243 Eur. J. Cancer 2017; 86:115-124 Eur J Cancer 2020 Dec 23;144:182-191. NCT01866319	RCT	mML - L2 - all population	pembrolizumab every 3 wk	ipilimumab	histologically confirmed, unresectable stage III or IV melanoma and had received no more than one previous systemic therapy for advanced disease	277 / 278	some concern	conclusif	demonstrated 31 % decrease in deaths (OS) (PE) demonstrated 42 % decrease in progression or deaths (PFS) (PE) suggested 32 % decrease in deaths (OS) (extension) suggested 39 % decrease in PFS (extension)
	pembrolizumab (10mg/kg) 2 weeks
	KEYNOTE-006 (2 week), 2015 Lancet 2017;390:1853-1862 N Engl J Med 2015;372:2521-32 Eur. J. Cancer 2018; 101:236-243 Lancet Oncol. 2019; 20:1239-1251 Eur. J. Cancer 2017; 86:115-124 Eur J Cancer 2020 Dec 23;144:182-191. NCT01866319	RCT	mML - L2 - all population	pembrolizumab every 2 wk	ipilimumab	histologically confirmed, unresectable stage III or IV melanoma and had received no more than one previous systemic therapy for advanced disease	279 / 278	some concern	conclusif	demonstrated 37 % decrease in deaths (OS) (PE) demonstrated 42 % decrease in progression or deaths (PFS) (PE) suggested 32 % decrease in deaths (OS) (extension) suggested 39 % decrease in PFS (extension)
versus placebo plus SoC
	ipilimumab plus SoC
	CA184-024, 2011 N Engl J Med 2011;364:2517-26 J Clin Oncol 2015;33:1191-6 NCT00324155	RCT	mML - L2 - all population	ipilimumab plus dacarbazine	dacarbazine plus placebo	patients with previously untreated metastatic melanoma, (stage III (unresectable) or stage IV melanoma) with measurable lesions; all patients received dacarbazine.	250 / 252	low	conclusif	demonstrated 28 % decrease in deaths (OS) (PE) demonstrated 24 % decrease in progression or deaths (PFS) (PE) suggested 31 % decrease in deaths (OS) (extension)
versus Standard of Care (SoC)
	nivolumab alone
	CheckMate 037, 2015 Lancet Oncol 2015;16:375-84 J Clin Oncol 2018;36:383-390 NCT01721746	RCT	mML - L2 - all population	nivolumab	chemotherapy (investigator’s choice)	patients with advanced melanoma (unresectable stage IIIC or IV metastatic melanoma, who progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAFV mutation-positive (second-line or later-line treatment).	272 / 133	high	inconclusive	inconclusive 5 % decrease in deaths (OS) (PE) suggested 2.4-fold increase in objective responses (ORR) (PE)
	pembrolizumab (10mg/kg)
	KEYNOTE-002 (10 mg/kg), 2015 Lancet Oncol. 2015; 16:908-18 Eur. J. Cancer 2017; 86:37-45 Eur. J. Cancer 2016; 67:46-54 Eur J Cancer 2020 Dec 23;144:182-191. NCT01704287	RCT	mML - L2 - all population	pembrolizumab	ICC (carboplatin plus paclitaxel, dacarbazine, paclitaxel alone or oral temozolomid)	18 years or older with unresectable stage III or stage IV melanoma, not amenable to local therapy; confirmed disease progression within 24 weeks of the last ipilimumab dose, previous BRAF or MEK inhibitor therapy or both,	181 / 179	some concern	conclusif	suggested 26 % decrease in deaths (OS) (PE) demonstrated 50 % decrease in progression or deaths (PFS) (PE)
	pembrolizumab (2mg/kg)
	KEYNOTE-002 (2 mg/kg), 2015 Lancet Oncol. 2015; 16:908-18 Eur. J. Cancer 2017; 86:37-45 Eur. J. Cancer 2016; 67:46-54 Eur J Cancer 2020 Dec 23;144:182-191. NCT01704287	RCT	mML - L2 - all population	pembrolizumab	ICC (carboplatin plus paclitaxel, dacarbazine, paclitaxel alone or oral temozolomid)	unresectable stage III or stage IV melanoma not amenable to local therapy; confirmed disease progression14 within 24 weeks of the last ipilimumab dose	180 / 179	some concern	conclusif	inconclusive 14 % decrease in deaths (OS) (PE) demonstrated 43 % decrease in progression or deaths (PFS) (PE)
mML - L2 - BRAF mutant metastatic/adv melanoma (mML) mML - 2nd line (L2) mML - L2 - BRAF mutant
versus placebo plus SoC
	pembrolizumab plus SoC
	KEYNOTE-022, 2019 Nat. Med. 2019; 25:941-946 Nat Med 2019 Jun;25(6):936-940. NCT02130466	RCT	mML - L2 - BRAF mutant	pembrolizumab, with dabrafenib and trametinib	placebo with dabrafenib and trametinib	patients with BRAFV600-mutant with advanced unresectable stage III or metastatic stage IV melanoma AND has received prior systemic therapy	60 / 60	low	inconclusive	inconclusive 34 % decrease in progression or deaths (PFS) (PE)

mML - NA - all population metastatic/adv melanoma (mML) mML - (neo)adjuvant (NA) mML - NA - all population

mML - NA - PDL1 positive metastatic/adv melanoma (mML) mML - (neo)adjuvant (NA) mML - NA - PDL1 positive

mML - L1 - all population metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - all population

mML - L1 - BRAF mutant metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - BRAF mutant

mML - L1 - BRAF wild metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - BRAF wild

mML - L2 - all population metastatic/adv melanoma (mML) mML - 2nd line (L2) mML - L2 - all population

mML - L2 - BRAF mutant metastatic/adv melanoma (mML) mML - 2nd line (L2) mML - L2 - BRAF mutant