immune checkpoint inhibition

systematic review meta-analysis network meta-analysis

Select advanced breast cancer (metastatic)gastric or gastro-oesophageal junction cancer (advanced)Head and neck cancerlung cancer (metastatic)melanomamultiple myelomarenal-cell carcinoma (advanced)urothelial carcinoma (advanced) adjuvant settingAll type of patientFirst line2nd line or moresecond line (or later)       anti PD-1anti PD1anti-CTLA-4anti-PD-1combinationIO + CTPD-L1 inhibitorsPD1 inhibitors atezolizumabdurvalumab + tremelimumab avelumab durvalumabipilimumabnivolumabpembrolizumab vs anti-CTLA-4vs anti-PD-1vs chemotherapyvs gp100vs ipilimumabvs placebovs placebo or controlvs standard of care       1st line2nd line2nd+ lineadjuvantmaintenance therapynonsquamous NSCLCPD-L1 negatifPD-L1 positiveplatinum failuresquamous NSCLC

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Group by Group by... nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition MA  in first nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in second nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in third	Description Synopsis Comparison Treatments Patients Characteristics Method Risk of bias References None Tools Indexation					Results Global trial result Main results All results All result tag NCT results	progression or death (progression free survival PFS) (54)death (overall survival) (53)Grade 3–5 drug-related AEs (25)vitiligo any grade (12)vitiligo grade 3-4 (12)objective response (ORR) (11)Adverse events leading to treatment discontinuation (10)recurrence free survival (6)serious drug-related adverse events (2)distant metastasis free survival (2) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	progression or death (progression free survival PFS)	death (overall survival)
gastric or gastro-oesophageal junction cancer (advanced)
nivolumab
ATTRACTION-2, 2017      NCT	nivolumab	placebo			Low risk of bias	suggesting
pembrolizumab
KEYNOTE-059 single-arm      NCT	pembrolizumab	nil				-
Keynote 061, 2018    NCT	pembrolizumab	paclitaxel	2L	2nd line PD-L1 positive	Risk of bias	negative
Head and neck cancer
nivolumab
Checkmate-141, 2016      NCT	nivolumab	standard treatment	2L	2nd line platinum failure	Risk of bias	conclusive
pembrolizumab
KEYNOTE-040    NCT	pembrolizumab	standard treatment	2L	2nd line	Risk of bias	suggesting
lung cancer (metastatic)
atezolizumab
IMpower150 (WT), 2018      NCT	atezolizumab + bevacizumab	bevacizumab (on top platinum-based CT)	1L	1st line nonsquamous NSCLC	Risk of bias	suggesting
IMpower150 (Teff), 2018        NCT	atezolizumab + bevacizumab	bevacizumab (on top platinum-based CT)	1L, Teff	1st line nonsquamous NSCLC	Risk of bias	suggesting
POPLAR Phase 2 atezolizumab, 2016    NCT	atezolizumab	docetaxel	2L	2nd+ line platinum failure	Risk of bias	negative
OAK, 2016      NCT	atezolizumab	docetaxel	2L	2nd+ line platinum failure	Risk of bias	suggesting
durvalumab
PACIFIC, 2017      NCT	durvalumab	placebo	maintenance	maintenance therapy	Low risk of bias	conclusive
ARCTIC PD-L1 negative, 2018    NCT	durvalumab + tremelimumab	Standard of Care	3L, PD-L1 negative			-
ipilimumab
Govindan, 2017      NCT	ipilimumab + chemotherapy	placebo + chemotherapy	1L		Low risk of bias	negative
Reck, 2016      NCT	ipilimumab + chemotherapy	placebo + chemotherapy	SCLC		Low risk of bias	-
phase 2 (phased ipilimumab), 2012	ipilimumab + chemotherapy	placebo + chemotherapy			Low risk of bias	-
nivolumab
CheckMate 017, 2015    NCT	nivolumab	docetaxel	2L, squamous	2nd+ line squamous NSCLC	Risk of bias	suggesting
CheckMate 057, 2015      NCT	nivolumab	docetaxel	2L, non squamous	2nd+ line nonsquamous NSCLC	Risk of bias	suggesting
CheckMate 026, 2016    NCT	nivolumab	platinum-based CT	1L, PDL1 positive	1st line PD-L1 positive	Risk of bias	negative
CheckMate 227 (nivolumab + CT), 2018    NCT	nivolumab + CT	platinum-based CT	1L, PDL1 negatif	1st line PD-L1 negatif		suggesting
CheckMate 227 (High Tumor Mutational Burden), 2018      NCT	nivolumab + ipilimumab	platinum-based CT	1L, hi TMB	1st line	Risk of bias	suggesting
pembrolizumab
Keynote 010 10mg, 2015      NCT	pembrolizumab 10mg	docetaxel	2L, PD-L1 positive	2nd+ line	Risk of bias	suggesting
Keynote 010 2mg, 2015      NCT	pembrolizumab 2mg	docetaxel	2L, PD-L1 positive	2nd+ line	Risk of bias	suggesting
Keynote 042 (>=1%), 2018    NCT	pembrolizumab	platinum-based CT	1L, PDL1 positive	1st line PD-L1 positive	Risk of bias	suggesting
Keynote 024, 2015      NCT	pembrolizumab	platinum-based CT	1L, PDL1 positive	1st line PD-L1 positive	Risk of bias	suggesting
Keynote 042 (>=50%), 2018    NCT	pembrolizumab	platinum-based CT	1L, PDL1 positive	1st line PD-L1 positive	Risk of bias	suggesting
Keynote 042 (>=20%), 2018    NCT	pembrolizumab	platinum-based CT	1L, PDL1 positive	1st line PD-L1 positive	Risk of bias	suggesting
KEYNOTE-021 phase 2, 2016      NCT	pembrolizumab + platinum-based CT	platinum-based CT	1L nonsquamous	1st line nonsquamous NSCLC	Exploratory	suggesting
Keynote 189, 2018      NCT	pembrolizumab + platinum-based CT	platinum-based CT	1L PD-L1 positive nonsquamous	1st line nonsquamous NSCLC	Low risk of bias	conclusive
Keynote 407, 2018      NCT	pembrolizumanb + CT	platinum-based CT	1L squamous	squamous NSCLC	Risk of bias	suggesting
melanoma
ipilimumab
Robert, 2011      NCT	ipilimumab + dacarbazine	dacarbazine	1L	1st line	Low risk of bias	conclusive
Hodi (ipi + gp100), 2010      NCT	ipi + gp100	gp100	2L	2nd line	Risk of bias	suggesting
Hodi (ipi alone), 2010      NCT	ipilimumab 3 mg/kg	gp100	2L	2nd line	Risk of bias	suggesting
EORTC 18071 (Eggermont), 2015        NCT	ipilimumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
nivolumab
CheckMate 037 (Weber), 2015      NCT	nivolumab	chemotherapy	2L, anti-CTLA-4 failure	2nd line	Risk of bias	suggesting
CheckMate 066 (Robert), 2015      NCT	nivolumab	dacarbazine	1L	1st line	Low risk of bias	conclusive
CheckMate 238, 2017      NCT	nivolumab	ipilimumab	adjuvant	adjuvant	Low risk of bias	conclusive
CheckMate 067 (nivo vs ipi), 2015      NCT	nivolumab	ipilimumab	1L	1st line	Low risk of bias	conclusive
CheckMate 067 (nivo + ipi vs ipi), 2015    NCT	nivolumab + ipilimumab	ipilimumab	1L	1st line	Low risk of bias	conclusive
Postow, 2015      NCT	nivolumab + ipilimumab	ipilimumab	1L	1st line	Exploratory	-
CheckMate 067 (nivo + ipi vs nivo), 2015      NCT	nivolumab + ipilimumab	nivolumab	1L	1st line	Exploratory	-
pembrolizumab
KEYNOTE 002 (10mg/kg Q3W), 2015      NCT	pembrolizumab 10mg/kg	chemotherapy	2L	2nd line	Exploratory	suggesting
KEYNOTE 002 (2mg/kg Q3W), 2015      NCT	pembrolizumab 2mg/kg	chemotherapy	2L	2nd line	Exploratory	suggesting
KEYNOTE-006 (every 2W), 2015      NCT	pembrolizumab (every 2W)	ipilimumab	1L	1st line	Risk of bias	suggesting
KEYNOTE-006 (every 3W), 2015      NCT	pembrolizumab (every 3W)	ipilimumab	1L	1st line	Risk of bias	suggesting
KEYNOTE-001, 2014      NCT	pembrolizumab 2mg/kg	pembrolizumab 10mg/kg	2L	2nd line	Exploratory	negative
KEYNOTE-054, 2018      NCT	pembrolizumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
multiple myeloma
pembrolizumab
KEYNOTE-185, 2018    NCT	pembrolizumab, lenalidomide, dexametahsone	lenalidomide, dexamethasone	not eligible for ASCT		Risk of bias	remark
KEYNOTE-183, 2018    NCT	pembrolizumab + pomadoline + dexamethasone	pomadoline + dexamethasone	rrMM		Risk of bias	negative
renal-cell carcinoma (advanced)
nivolumab
Chekmate 025 (Motzer), 2015      NCT	nivolumab	everolimus	2L		Risk of bias	suggesting
CheckMate-214, 2017      NCT	nivolumab + ipilimumab	sunitinib	1L		Risk of bias	conclusive
urothelial carcinoma (advanced)
atezolizumab
IMvigor211 (IC2/3)      NCT	atezolizumab	chemotherapy	2nd line, IC2/3	2nd line	Risk of bias	suggesting
IMVIGOR-130 (monotherapy)    NCT	atezolizumab	control	first line	1st line	Risk of bias	remark
IMvigor210 single-arm      NCT	atezolizumab	nil	1st and 2nd line	1st line 2nd line	Exploratory	-
durvalumab
durvalumab phase 1/2 single-arm	durvalumab	nil	2nd line	2nd line	Exploratory	-
nivolumab
Checkmate 275 single-arm      NCT	nivolumab	nil	2nd line	2nd line	Exploratory	-
pembrolizumab
KEYNOTE-052, 2017 single-arm      NCT	pembrolizumab			1st line	Risk of bias	-
KEYNOTE-045, 2017    NCT	pembrolizumab	chemotherapy	2nd line	2nd line	Risk of bias	suggesting
Keynote 361 monotherapy    NCT	pembrolizumab	chemotherapy	first line			remark