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 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 placebo
	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)
	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...
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)
mML - L1 - BRAF mutant metastatic/adv melanoma (mML) mML - 1st line (L1) mML - L1 - BRAF mutant
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 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 ipilimumab alone
	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 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