Table 2. Phase II/III trials with multi-targeted TKI.
| TREATMENT | REFERENCE/ STUDY PHASE | PATIENTS | RESPONSES | SURVIVAL |
| VANDETANIB | ||||
| Vandetanib vs. gefitinib | Natale RB. 2009. Randomized phase II |
168 (previously treated) |
Vandetanib: 8% ORR, 45% SD Gefitinib: 1% PR, 34% SD |
Vandetanib: PFS 11 weeks Gefitinib: PFS 8 weeks (HR=0.69; p=0.025) |
| Paclitaxel+carboplatin (PC) vs. PC+ vandetanib (PCV) | Heymach JV. 2008. Randomized phase II |
181 (first-line treatment) |
PC: ORR 32% PCV: ORR 25% |
PC: PFS 23 weeks PCV:PFS 24 weeks (HR=0.76; p=0.98) |
| Docetaxel+vandetanib (DV) vs. Placebo+vandetanib (PlV) (ZODIAC) | Herbst RS. 2010. Phase III |
1391 (second-line treatment) |
DV: ORR 17% PlV: ORR 10% (p=0.0001) |
PFS: 4 months (DV) vs. 3.2 months (PIV) (HR=0.79; p=0.024) OS: 10.3 months (DV) vs. 9.9 months (PIV) (HR=0.95; p=0.371) |
| Pemetrexed+vandetanib (PV) vs. Placebo+vandetanib (PlV) (ZEAL) | De Boer R. 2009. Phase III |
534 (second-line treatment) |
PV: ORR 19.1% PlV: ORR 7.9% (p<0.001) |
PFS: 17.6 weeks (PIV) vs. 11.9 weeks (PlV) (HR=0.86; p=0.108) OS: 10.5 months (PIV) vs. 9.2 months (PlV) (HR=0.86; p=0.219) |
| Vandetanib (V) vs. placebo (Pl) (ZEPHYR) | Lee J. 2010. Phase III |
924 (previously treated with EGFR TKI) |
V: ORR 2.6% Pl: ORR 0.7% (p=0.028) |
PFS: 12.2 weeks (V) vs. 8.4 weeks (E) (HR=0.63; p<0.0001) OS: 8.5 months (V) vs. 7.8 months (E) (HR=0.95; p=0.527) |
| Vandetanib (V) vs. erlotinib (E) (ZEST) | Natale RB. 2009. Phase III |
1240 (previously treated) |
V: ORR 12% E: ORR 12% |
PFS: 11.3 weeks (V) vs. 8.9 weeks (E) (HR=0.96; p=0.72) OS: 6.9 months (V) vs. 7.8 months (E) (HR=1.01; p=0.93) |
| CEDIRANIB | ||||
| Paclitaxel+carboplatin+ Cediranib (PCCe) vs. Paclitaxel+carboplatin+ Placebo (PCPl) (BR.24) | Goss GD. 2009. Phase II-III |
296 (first-line treatment) |
PCCe: ORR 38% PCPl: ORR 16% (p<0.001) |
PFS: 5.6 months (PCCe) vs. 5 months (PCPl) (HR=0.77; p=0.13) OS: 10.5 months (PCCe) vs. 10.1 months (PCPl) (HR=0.78; p=0.11) |
| Cisplatin+ gemcitabine (CG) vs. CG+cediranib (CGCe) | Dy GK. 2010. Randomized phase II |
87 (first-line treatment) |
CG: ORR 20% CGCe: ORR 18% (p=1) |
PFS: 6.3 months (CG) vs. 4.5 months (CGCe) (HR=0.69; p=0.5) OS: 11.8 months (CG) vs. 9.9 months (CGCe) (HR=0.66; p=0.16) |
| SUNITINIB | ||||
| Sunitinib 50 mg/day schedule 4/2 | Socinski MA. 2008 Phase II |
63 (previously treated) |
ORR 11.1% SD 28.6% |
Median PFS 12 weeks Median OS 23.4 weeks |
| Sunitinib 37.5 mg/day continuous daily dosing | Novello S. 2009 Phase II |
47 (previously treated) SORAFENIB |
ORR 2.1% SD ≥ 8 weeks 23.4% |
Median PFS 11.9 weeks Median OS 37.1 weeks |
| Sorafenib | Blumenschein GR. 2009. Phase II |
54 (previously treated) |
ORR 0% SD 59% |
Median PFS 2.7 months Median OS 6.7 months |
| Paclitaxel+carboplatin (PC) vs. PC+ sorafenib (PCS) (ESCAPE) | Scagliotti G. 2010. Phase III. |
181 (first-line treatment) |
PC: ORR 27.4% PCS: ORR 24% |
PFS: 4.6 months (PC) vs. 5.4 months (PCS) (HR=0.99; p=0.43) OS: 10.7 months (PC) vs. 10.6 months (PCS) (HR=1.15; p=0.915) |
| AXITINIB | ||||
| Axitinib | Schiller JH. 2009 Phase II |
32 (first-line and previously treated) |
PR 9% SD 32% |
Median PFS 4.9 months Median OS 14.8 months |
| VATALANIB | ||||
| Vatalanib once daily Vatalanib twice daily | Gauler TC. 2007 Phase II |
110 (second-line) |
Once daily: ORR 2%, SD ≥4 weeks 39% Twice daily: ORR 7%, SD ≥4 weeks 46% |
Once daily: median PFS 2.2 months, median OS 7.3 months. Twice daily: median PFS 7.3 months, median OS 7.4 months. |
| MOTESANIB | ||||
| Paclitaxel+carboplatin+ Motesanib 125 md/day continuous (PCM125) PC+motesanib 75 mg bid five days and two weeks off (PCM75) PC+bevacizumab(PB) | Blumenschein GR. 2010. Randomized phase II |
181 (first-line treatment) |
PCM125: ORR 30% PCM75: ORR 23% PB: ORR 37% |
PCM125: median PFS 8.4 months, median OS 15.2 months PCM75: median PFS 6.2 months, median OS 13.9 months PB: median PFS 9 months, median OS 15.2 months |
| PAZOPANIB | ||||
| Pazopanib | Altorki N. 2010. Phase II |
35 Stage I/II. Preoperative treatment |
86% tumor volume reduction 5.7% tumor volume reduction ≥ 50% 3% PR (RECIST) |
NA |
CT: chemotherapy; EGFR: epidermal growth-factor receptor; TKI: tyrosine-kinase inhibitor; ORR: overall response rate; SD: stable disease; PFS: progression-free survival; OS: overall survival; NA: not available