Table 5: The update results of published clinical trials targeting EGFR signaling in urothelial carcinoma patients.

Study agentsPts no.ORR (%)Recommendation

EGFR signaling
 Cetuximab + paclitaxel versus cetuximab3928.5 versus 18The combination merits further evaluation [38]
 Geftinib + Gemcitabine, cisplatin5842.6% The combination of cisplatin, gemcitabine, and gefitinib is well tolerated, and the addition of gefitinib does not appear to improve response rate or survival [39, 40]
 Geftinib316.5 Geftinib (ZD1839) is ineffective as a second-line agent for urothelial carcinoma [41]

EGFR and ErbB2 signaling
 Lapatinib59ORR (1.7%) and
SD (31%)
A negative result, but clinical benefit (ORR and SD) is correlated with EGFR overexpression ( 𝑃 = 0 . 0 2 9 ), and, to some extent, HER-2 overexpression [42]

EGFR, VEGFR, and RET signaling
Vandetanib plus docetaxel versus placebo plus docetaxel142ORR, 7 versus 11 ( 𝑃 = 0 . 5 6 ); PFS,
2.6 m versus 1.6 m ( 𝑃 = 0 . 9 3 9 ); OS, 5.9 m versus 7.0 m ( 𝑃 = 0 . 3 4 7 )
The addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS [43]

ORR: objective response rate; SD: stable disease, PFS: progression-free survival; OS: overall survival; VEGFR: vascular endothelial growth factor receptor; RET: rearranged during transfection.