Table 5.
Reported and ongoing trials of targeted agents as second-line therapy in metastatic bladder cancer
| Table 5a. Reported trials of targeted agents with chemotherapy as second-line therapy in metastatic bladder cancer | ||||||||
|---|---|---|---|---|---|---|---|---|
| Author | Year | Agent | Target | Chemotherapy | Study type | n | RR% | OS (months) |
| Theodore [93] | 2005 | Lonafarnib | Farnesyltransferase | Gemcitabine | Phase II | 31 | 32 | NR |
| Choueiri [91] | 2012 | Vandetanib | VEGFR, EGFR, RET | Docetaxel and vandetanib | Randomized phase II | 142 | 7 | 5.56 |
| Docetaxel and placebo | 11 | 7.39 | ||||||
| Wong [92] | 2012 | Cetuximab | EGFR | Pactilaxel and cetuximab alone | Randomized phase II | 39 | 25 | 10.5 |
| 0 | 1.3 | |||||||
| Table 5b. Reported trials of targeted agents with single-agent second-line therapy in metastatic bladder cancer | ||||||||
| Author | Year | Agent | Target | Chemotherapy | Study type | n | RR% | OS (months) |
| Gomez-Abuin [94] | 2007 | Bortezomib | Proteasome inhibitor | None | Phase II | 20 | 0 | NR |
| Rosenberg [96] | 2008 | Bortezomib | Proteasome inhibitor | None | Phase II | 25 | 0 | 5.7 |
| Wulfing [97] | 2009 | Lapatinib | HER2/EGFR | None | Phase II | 59 | 3 | 4.5 |
| Petrylak [98] | 2009 | Gefitinib | EGFR | None | Phase II | 31 | 3 | 3 |
| Dreicer [90] | 2009 | Sorafenib | B-Raf,c-Raf, VEGFR-2/3, PDGFR-b | None | Phase II | 27 | 0 | 6.8 |
| Gallagher [89] | 2010 | Sunitinib | VEGFR-1/2, C-KIT, PDGFR a/b, FLT3, RET | None | Phase II | 45 | 7 | 6.9 |
| Twardowski [99] | 2010 | Aflibercept | VEGF, PDGF | None | Phase II | 22 | 4.5 | NR |
| Cheung [100] | 2010 | Vorinostat | SAHA: histone deacetylase | None | Phase II | 14 | 0 | 4.3 |
| Stadler [95] | 2011 | Volasertib | Polo-like kinase 1 | None | Phase II | 31 | 19 | NR |
| Milowsky [101] | 2011 | Everolimus | PI3K/Akt/mTOR | None | Phase II | 45 | 5 | 10.5 |
| Pili [102] | 2011 | Pazopanib | VEGFR1/2/3, PDGFR a/b,c-Kit | None | Phase II | 19 | 0 | NR |
| Necchi [103] | 2012 | Pazopanib | VEGFR1/2/3, PDGFR a/b,c-Kit | None | Phase II | 41 | 17 | 4.7 |
| Lerner [104] | 2012 | Tamoxifen | ER-B | None | Phase II | 28 | NR | NR |
| Milowsky [105] | 2013 | Dovitinib | FGFR3 | None | Phase II | 44 | 0 | NR |
| Table 5c. Ongoing trials of targeted agents with chemotherapy as second-line therapy in metastatic bladder cancer | |||||||
|---|---|---|---|---|---|---|---|
| PI/group | Start year | Agent | Target | Chemotherapy | Study type | Target enrollment | Clinicaltrials.gov ID |
| Quinn [107] | 2011 | Lapatinib | HER2/EGFR | Docetaxel | Phase II | 40 | NCT01382706 |
| ImClone [109] | 2011 | Ramucirumab | VEGFR2 | Docetaxel | Three-arm randomized phase II | 138 | NCT01282463 |
| Otto [110] | 2011 | Pazopanib | VEGFR1/2/3, PDGFR a/b,c-Kit | Vinflunine | Phase I/II | NR | NCT01265940 |
| Hahn [111] | 2013 | OGX-427 | Hsp27 | Docetaxel | Randomized phase II | 200 | NCT01780545 |
| Table 5d. Ongoing trials of targeted agents as single-agent second-line therapy in metastatic bladder cancer | |||||||
| PI/group | Start year | Agent | Target | Chemotherapy | Study type | Target enrollment | Clinicaltrials.gov ID |
| Hoffman [112] | 2001 | Trastuzumab | HER2 | None | Phase II | 5 | NCT02013765 |
| Quinn [113] | 2006 | Eribulin | Tubulin | None | Phase I/II, renal dysfunction | 82 | NCT00365157 |
| Fowl es [106] | 2009 | Lapatinib | HER2/EGFR | None | Randomized phase II/III | 204 | NCT00949455 |
| Fernandez [114] | 2010 | AEZS-108 | LHRH linked to doxorubicin | None | Phase I/II | 64 | NCT01234519 |
| Apolo [115] | 2011 | TRC105 | CD 105 | None | Phase II | 45 | NCT01328574 |
| Bajorin [108] | 2012 | BKM120 | PI3K | None | Phase II | 35 | NCT01551030 |
| Apolo [116] | 2012 | Cabozantinib | VEGFR/cMET | None | Phase II | 55 | NCT01688999 |
| Necchi [117] | 2012 | PF-03446962 | TGFβR/ALKl | None | Phase II | 45 | NCT01620970 |
| Wood [53] | 2013 | Dendritic-cell vaccine | Ad/HER2/neu | None | Phase I | 65 | NCT01730118 |
| Agensys [118] | 2013 | ASG-15ME | SLITRK6 | None | Phase I | 45 | NCT01963052 |
ALK1, activin receptor-like kinase 1; EGFR, epidermal growth factor receptor; ER, estrogen receptor; FGFR, fibroblast growth factor receptor; 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; SAHA, suberanilohydroxamic acid; TGFβR, transforming growth factor β receptor; VEGFR, vascular endothelial growth factor receptor.