lung cancer (metastatic)

systematic review meta-analysis network meta-analysis

Select ALK inhibitorsangiogenesis inhibitorsCDK (cyclin-dependent kinase) inhibitorEGFR inhibitors immune checkpoint inhibitionchemotherapyTaxanes ALK positive patientsAll type of patientFirst line2nd line or more       3-weekly docetaxelALK inhibitorsanti angiogenesis antibodyanti-CTLA-4anti-PD-1CDK4 and CDK6 selective CDK inhibitorcombinationdocetaxel-based doubletIO + CTmonoclonal antibodyPD-L1 inhibitorspemetrexed alonepemetrexed doubletTKIweekly docetaxel abemaciclib afatinibaflibercept alectinibatezolizumabbrigatinibceritinibdacomitinibmotesanib osimertinib vandetanib avelumab bevacizumabcetuximabcrizotinib docetaxeldurvalumaberlotinibgefitinibipilimumabnivolumabpazopanibpembrolizumabpemetrexed sorafenibsunitinib vs chemotherapyvs crizotinibvs placebovs standard of care       1st line2nd line2nd+ linecrizotinib failureEGFR mutationsmaintenance 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) (57)death (overall survival) (55)objective response (ORR) (27)Grade 3–5 drug-related AEs (4) 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)
ALK inhibitors
alectinib
ALUR, 2018    NCT	alectinib	chemotherapy	2L	2nd line crizotinib failure	Exploratory	suggesting
ALEX, 2017      NCT	alectinib	crizotinib	1L	1st line	Risk of bias	conclusive
ceritinib
ASCEND-4, 2017      NCT	ceritinib	chemotherapy	1L	1st line nonsquamous NSCLC	Risk of bias	suggesting
ASCEND 5, 2017      NCT	ceritinib	pemetrexed or docetaxel	2L after crizotinib failure	2nd line crizotinib failure		-
crizotinib
Shaw, 2013      NCT	crizotinib	chemotherapy	2L	2nd line	Risk of bias	suggesting
PROFILE 1014, 2014        NCT	crizotinib	chemotherapy	1L	1st line nonsquamous NSCLC	Risk of bias	suggesting
angiogenesis inhibitors
not classified
Hanna, 2013						-
Heymach, 2008						-
Reck, 2014      NCT	Docetaxel plus nintedanib	docetaxel plus placebo			Low risk of bias	-
aflibercept
Ramlau, 2012	Aflibercept and Docetaxel	Docetaxel			Low risk of bias	-
bevacizumab
Reck, 2010	bevacizumab					-
Herbst, 2011	bevacizumab + erlotinib	erlotinib alone				-
Sandler, 2006	bevacizumab	platinum based CT				-
Johnson, 2004	bevacizumab	platinum based CT				-
Nishio, 2009	bevacizumab	platinum based CT				-
Herbst, 2007	bevacizumab	platinum based CT				-
ceritinib
Laurie, 2014	cediranib	carboplatin and paclitaxel				-
Goss, 2010	cediranib	carboplatin and paclitaxel				-
Dy, 2013	cediranib	gemcitabine and carboplatin				-
docetaxel
REVEL, 2014      NCT	ramucirumab + docetaxel	docetaxel alone			Low risk of bias	-
motesanib
Scagliottib MONET1, 2012	motesanib plus carboplatin/paclitaxel					-
pazopanib
Scagliotti, 2013	pazopanib	pemetrexed				-
sorafenib
Wakelee, 2012	sorafenib					-
Paz-Ares, 2012	sorafenib					-
Spigel, 2011	sorafenib and erlotinib	erlotinib				-
Scagliotti, 2010	sorafenib	placebo				-
sunitinib
Groen, 2013	sunitinib	erlotinib			Low risk of bias	-
Scagliottia, 2012	Sunitinib plus erlotinib	erlotinib				-
Heist CALGB 30704 (Alliance): , 2014	sunitinib	pemetrexed				-
vandetanib
Aisner, 2013	vandetanib					-
Ahn, 2013	vandetanib maintenance					-
de Boer, 2011	Vandetanib plus pemetrexed					-
Natale, 2009	Vandetanib versus gefitinib				Low risk of bias	-
Natale, 2011	Vandetanib	gefitinib			Low risk of bias	-
Lee ZEPHYR, 2012	Vandetanib	placebo				-
Heymach, 2007	vandetanib plus docetaxel	placebo plus docetaxel				-
CDK (cyclin-dependent kinase) inhibitor
abemaciclib
JUNIPER, 2018      NCT	abemaciclib	erlotinib	2nd line		Risk of bias	remark
chemotherapy
not classified
Scagliotti (pemetrexed vs bortezomib), 2010	pemetrexed	bortezomib				-
Scagliotti, 2010	bortezomib and pemetrexed	pemetrexed				negative
Chiappori, 2010	enzastaurin plus pemetrexed	pemetrexed				negative
Schiller, 2010	matuzumab plus pemetrexed	pemetrexed				negative
pemetrexed
Chen, 2008	pemetrexed	docetaxel				-
Hanna, 2004	pemetrexed	docetaxel				-
Li, 2012	pemetrexed	docetaxel				-
Sun, 2013      NCT	pemetrexed	docetaxel				-
Jose, 2011	pemetrexed plus carboplatin	docetaxel plus carboplatin				-
Socinski, 2010      NCT	pemetrexed plus carboplatin	docetaxel plus carboplatin				-
Smit, 2009	pemetrexed plus carboplatin	pemetrexed				suggesting
vandetanib
De Boer, 2011	vandetanib plus pemetrexed	pemetrexed				negative
EGFR inhibitors
not classified
SQUIRE    NCT						-
INSPIRE    NCT						-
afatinib
LUX-LUNG 3, 2015	afatinib	cisplatin-based chemotherapy				-
LUX-LUNG 6, 2015	afatinib	cisplatin-based chemotherapy				-
cetuximab
Lynch, 2010	cetuximab	CT			Risk of bias	negative
Butts, 2007	cetuximab	CT alone				-
FLEX (Pirker), 2009      NCT	cetuximab + CT	CT alone				suggesting
Rosell, 2008	cetuximab + CT	CT alone				-
dacomitinib
ARCHER 1050      NCT	dacomitinib	gefitinib				-
erlotinib
OPTIMAL	erlotinib	Platinum-based CT		EGFR mutations	Risk of bias	suggesting
EUTRAC	erlotinib	Platinum-based CT		1st line EGFR mutations	Risk of bias	suggesting
TITAN	erlotinib	Platinum-based CT		2nd line	Risk of bias	negative
TRIBUTE (Herbst)	erlotinib + Platinum-based CT	Platinum-based CT		1st line		negative
Gatzemeier	erlotinib + Platinum-based CT	Platinum-based CT		1st line		negative
Mok	erlotinib + Platinum-based CT	Platinum-based CT		1st line		suggesting
SATURN (Cappuzzo)	erlotinib + Platinum-based CT	Platinum-based CT		maintenance therapy		suggesting
Boutsikou	erlotinib + Platinum-based CT	Platinum-based CT		1st line		negative
Lee	erlotinib + Platinum-based CT	Platinum-based CT		2nd line		suggesting
Stinchcombe	erlotinib + Platinum-based CT	Platinum-based CT				negative
FASTACT-2 (Wu)	erlotinib + Platinum-based CT	Platinum-based CT		1st line		suggesting
gefitinib
West Japan	gefitinib					-
Northeast Japan	gefitinib					-
CTONG0806 (Yang), 2013	gefitinib					-
NEJ002, 2013	gefitinib	carboplatin-paclitaxel	1L			-
Maemondo, 2010	gefitinib	carboplatin-paclitaxel	2L			-
IPASS (Mok), 2009      NCT	gefitinib	carboplatin-paclitaxel	1L			-
IPASS	gefitinib	carboplatin/paclitaxel	1L			-
WJTOG3405 (Mitsudomi), 2010	gefitinib	cisplatin plus docetaxel				-
WJTOG0203 (Takeda), 2010	gefitinib	continued platinum-doublet chemotherapy				-
ISTANA (Lee), 2010	gefitinib	docetaxel	2L			suggesting
V-15-32 (Maruyama), 2008	gefitinib	docetaxel	2L			suggesting
INTEREST (Kim), 2008	gefitinib	docetaxel	2L			negative
SIGN (Cufer), 2006	gefitinib	docetaxel	2L			negative
IFCT-0301 study (Morère), 2010	gefitinib	docetaxel				-
Kris, 2003	gefitinib	gefitinib	2L		Low risk of bias	-
First Signal	gefitinib	gemcitabine and cisplatin	1L			-
INTACT 2, 2004	gefitinib paclitaxel and carboplatin	paclitaxel and carboplatin	1L		Low risk of bias	-
NCIC CTG BR19 (Goss), 2013	gefitinib	placebo			Low risk of bias	-
INFORM; C-TONG 0804, 2012      NCT	gefitinib	placebo				-
EORTC 08021/ILCP 01/03, 2011      NCT	gefitinib	placebo	2L			-
Goss, 2009	gefitinib	placebo	1L			-
SWOG S0023 (Kelly), 2008	gefitinib	placebo				-
ISEL, 2006	gefitinib	placebo	2L			-
Tsuboi, 2005	gefitinib	placebo				-
INTACT 1.	gefitinib + gemcitabine/cisplatin	placebo + gemcitabine / cisplatin	1L		Low risk of bias	-
INVITE (Crinò), 2008      NCT	gefitinib	vinorelbine	1L			-
osimertinib
FLAURA, 2017      NCT	osimertinib	placebo	1L		Low risk of bias	suggesting
AURA 3, 2017    NCT	osimertinib	platinum-based therapy plus pemetrexed	2L			suggesting
immune checkpoint inhibition
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
Reck, 2016      NCT	ipilimumab + chemotherapy	placebo + chemotherapy	SCLC		Low risk of bias	-
Govindan, 2017      NCT	ipilimumab + chemotherapy	placebo + chemotherapy	1L		Low risk of bias	negative
phase 2 (phased ipilimumab), 2012	ipilimumab + chemotherapy	placebo + chemotherapy			Low risk of bias	-
nivolumab
CheckMate 057, 2015      NCT	nivolumab	docetaxel	2L, non squamous	2nd+ line nonsquamous NSCLC	Risk of bias	suggesting
CheckMate 017, 2015    NCT	nivolumab	docetaxel	2L, squamous	2nd+ line squamous 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
Taxanes
not classified
Herbst						suggesting
Gebbia						-
Pectasides						suggesting
Takeda						suggesting
Pallis						suggesting
Heymach						-
Wachters						negative
Segawa						-
TAX 320 75mg/m2, 2000	docetaxel D75					-
TAX 317 (Shepherd) 75mg/m2, 2000	docetaxel D75					-
docetaxel
TAX 317 (Shepherd) 100mg/m2, 2000	docetaxel					-
TAX 320 100mg/m2, 2000	docetaxel					-
DISTAl 01 (Gridelli) , 2004	weekly docetaxel	3-weekly docetaxel				-
Camps	weekly docetaxel	3-weekly docetaxel				-
Schuette	weekly docetaxel	3-weekly docetaxel				-
Gervais	weekly docetaxel	3-weekly docetaxel				-
Lai	weekly docetaxel	3-weekly docetaxel				-
Chen	weekly docetaxel	3-weekly docetaxel				-
Esteban, 2003	paclitaxel 80mg/m2	m2docetaxel 36 mg/				-