Table 4.

Reported and ongoing trials of targeted agents as first-line therapy in metastatic bladder cancer

Table 4a. Reported trials of targeted agents with chemotherapy as first-line therapy in metastatic bladder cancer
Author	Year	Agent	Target	Chemotherapy	Study type	n	RR%	OS (months)
Hussain [63]	2007	Trastuzumab	HER2	Paclitaxel, gemcitabine, carboplatin	Phase II	44	70	14.1
Philips [64]	2009	Gefitinib	EGFR	Gemcitabine and cisplatin	Phase II	54	43	15.1
Hahn [45]	2011	Bevacizumab	VEGF	Gemcitabine and cisplatin	Phase II	43	72	19.1
Menhert [65]	2011	Sorafenib	B-Raf,c-Raf, VEGFR-2/3, PDGFR-b	Gemcitabine and cisplatin	Phase II	17	30	NR
Krege [66]	2011	Sorafenib	B-Raf,c-Raf, VEGFR-2/3, PDGFR-b	Gemcitabine and cisplatin	Phase II	40	53	11.3
Grivas [67]	2012	Cetuximab	EGFR	Gemcitabine and cisplatin + cetuximab; gemcitabine and cisplatin alone	Randomized phase II	88	57	14
Balar [62■■]	2013	Bevacizumab	VEGF	Gemcitabine and carboplatin	Randomized phase II (1 : 2)	51	63	14
Galsky [39]	2013	Sunitinib	VEGFR-1/2, C-KIT, PDGFR a/b,FLT3, RET	Gemcitabine and cisplatin	Phase II	36	49	13.9
Table 4b. Reported trials of targeted agents as single-agent first-line therapy in metastatic bladder cancer
Author	Year	Agent	Target	Chemotherapy	Study type	n	RR%	OS (months)
Bellmunt [68]	2010	Sunitinib	VEGFR-1/2, C-KIT, PDGFR a/b, FLT3, RET	None	Phase II	38	8	8.1
Quinn [61]	2010	Eribulin	Tubulin	None	Phase II	37	38	9.4
Sridhar [69]	2011	Sorafenib	B-Raf,c-Raf, VEGFR-2/3, PDGFR-b	None	Phase II	17	0	5.9

Table 4c. Ongoing trials of targeted agents as first-line therapy with chemotherapy in metastatic bladder cancer
PI/group	Start year	Agent	Target	Chemotherapy	Study type	Target enrollment	Clinicaltrials.gov ID
Hoffman [73]	2001	Trastuzumab	HER2	Gemcitabine and cisplatin	Phase II	13	NCT02006667
Oudard [74]	2004	Trastuzumab	HER2	Gemcitabine and cisplatin or carboplatin	Randomized phase II	61	NCT01828736
Chester [75]	2008	Temsirolimus	mTOR	Gemcitabine and cisplatin	Phase I/II	99	NCT01090466
EORTC [76]	2008	Lapatinib	HER2/EGFR	Gemcitabine and cisplatin	Phase I	25	NCT00623064
Rosenberg [77]	2009	Bevacizumab	VEGF	Gemcitabine and cisplatin	Randomized phase III	500	NCT00942331
Eisai INC [78]	2010	Eribulin	Tubulin	Gemcitabine and cisplatin	Phase Ib/II	95	NCT01126749
Miller [79]	2010	Panitumumab	EGFR	Gemcitabine and cisplatin	Randomized phase II	124	NCT01374789
Salvioni [80]	2010	Sorafenib	B-Raf,c-Raf, VEGFR-2/3, PDGFR-b	Gemcitabine and cisplatin	Phase II	45	NCT01222676
Bajorin [81]	2010	Everolimus	PI3K/Akt/mTOR	Gemcitabine and split-dose cisplatin	Phase I	30	NCT01182168
Petrylak [71]	2011	OGX-427	HSP27	Gemcitabine and cisplatin	Randomized phase II	180	NCT01454089
Wong [82]	2011	ALT-801	p53	Gemcitabine and cisplatin	Phase I/II	76	NCT01326871
Galsky [72]	2012	Ipilimumab	CTLA-4	Gemcitabine and cisplatin	Phase II	36	NCT01524991
Ullen [83]	2012	Sorafenib	B-Raf,c-Raf, VEGFR-2/3, PDGFR-b	Vinflunine	Phase I	24	NCT01844947
Flag [84]	2013	Trebananib	Ang1, Ang2	Docetaxel	Phase II	38	NCT01907308
Table 4d. Ongoing trials of targeted agents for cisplatin-ineligible patients as first-line therapy in metastatic bladder cancer
PI/group	Start year	Agent	Target	Chemotherapy	Study type	Target enrollment	Clinicaltrials.gov ID
Oudard [74]	2004	Trastuzumab	HER2	Gemcitabine and cisplatin or carboplatina	Randomized phase II	61	NCT01828736
Jones [70]	2010	Lapatinib	HER2/EGFR	Gemcitabine and carboplatin	Phase II	122	NCT01191892
Galsky [85]	2010	Everolimus	PI3K/Akt/mTOR	Paclitaxel	Phase II	68	NCT01215136
Apolo [86]	2011	Lenalidomide	Apoptosis, antiangiogenesis and immune modulation	Gemcitabine and carboplatin	Phase I	42	NCT01352962
Bajorin [87]	2012	Pazopanib	VEGFR1/2/3, PDGFR a/b,c-Kit	Gemcitabine	Phase II	45	NCT01622660

^aChemotherapy is gemcitabine and cisplatin or gemcitabine and carboplatin based on creatinine clearance.

EGFR, epidermal growth factor receptor; EORTC, European Organisation for Research and Treatment of Cancer; HER, human epidermal growth factor receptor; mTOR, mammalian target of rapamycin; n, number of patients enrolled; NR, not reported; OS, overall survival; PDGFR, platelet-derived growth factor receptor; PI, principal investigator; RR, response rate; SLITRK6, SLIT and TRK-like family member 6; VEGFR, vascular endothelial growth factor receptor.