Table 2. Trials evaluating antiangiogenic TKIs in combination with chemotherapy in locally advanced or metastatic NSCLC as first or second-line therapy.
| Study | Design | Patients | n | Experimental arm | Control arm | mPFS/mTTP | mOS | ORR | PE, p value |
|---|---|---|---|---|---|---|---|---|---|
| First-line | |||||||||
| ESCAPE [49] | Phase III | NSCLC | 926 | Pac+Car+Sor | Pac+Car | 4.6 vs 5.4 m | 10.7 vs 10.6 m | 27.4% vs 24.0% | OS; p = 0.915 |
| NEXUS [50] | Phase III | nsNSCLC | 772 | Gem+Cis+Sor | Gem+Cis | 6.0 vs 5.5 m | 12.4 vs 12.5 m | 28% vs 26% | OS; p = 0.401 |
| MONET1 [51] | Phase III | nsNSCLC | 1090 | Pac+Car+Mot | Pac+Car | 5.6 vs 5.4 m | 13.0 vs 11.0 m | 40% vs 26% | OS; p = 0.14 |
| NCT00369070 [52] | Phase II | nsNSCLC | 186 | Pac+Car+Mot | Pac+Car+Bev | 7.7 (125 mg qd) vs 5.8 (75 mg bid) vs 8.3 m | 14.0 (125 mg qd) vs 12.8 (75 mg bid) vs 14.0 | 30% vs 23% vs 37% | ORR |
| NCIC IND [53] | Phase I | NSCLC | 20 | Pac+Car+Ced | 7.6 m | 45% | |||
| BR24 [54] | Phase II | NSCLC | 251 | Pac+Car+Ced | Pac+Car | 5.6 vs 5.0 m | PFS; p = 0.08 | ||
| BR29 [55] | Phase III | NSCLC | 306 | Pac+Ced | Pac | 5.5nvs 5.5 m | 12.2 vs 12.1 m | 52% vs 34% | OS; p = 0.72 |
| N0528 [56] | Phase II | NSCLC | 87 | Gem+Cb+Ced | Gem+Car | 6.3 vs 4.5 m | 12 vs 9.9 m | 19% vs 20% | ORR; p = 1.0 |
| Heymach [57] | Phase II | NSCLC | 108 | Pac+Cb+Van | Pac+Car | 24 vs 23 w | 10.2 vs 12.6 m | 32% vs 25% | PFS; p = 0.098 |
| Aisner et al. [58] | Phase II | NSCLC | 162 | Pac+Cb+Van→van | Pac+Car+Van→Plac | 4.5 vs 4.2 m | 9.8 vs 9.4 m | PFS; p = 0.07 | |
| Scagliotti et al. [59] | Phase II | nsNSCLC | 106 | Pem+Paz | Pem+Cis | 25.0 vs 22.9 w | HR: 1.22; P = 0.55 | 23% vs 34% | PFS; p = 0.26 |
| Belani et al. [60] | Phase II | nsNSCLC | 170 | Pem+Cis+Axi | Pem+Cis+Axi | 8.0 (d1-21) vs 7.9 (d2-19) vs 7.1 m | 16.6 (d1-21) vs 14.7 (d2-19) vs 15.9 m | 45.5% (d1-21) vs 39.7% (d12-19) vs 26.3% | PFS; p = 0.36 (d1-21); p = 0.54 (d2-19) |
| Twelves et al. [61] | Phase II | nsNSCLC | 118 | Pac+Car+Axi | Pac+Car+Bev | 5.7 vs 6.1 m | 10.6 vs 13.3 m | 29.3% vs 43.3% | PFS; p = 0.64 |
| Ramalingam et al. [62] | Phase II | nsNSCLC | 138 | Pac+Car+Lin | Pac+Car | 8.3 (7.5 mg) vs 7.3 (12.5 mg) vs 5.4 m | 11.4 (7.5mg) vs 13.0 (12.5 mg) vs 11.3 m | 8.3 (7.5 mg) vs 7.3 (12.5 mg) vs 5.4 m | PFS; p = 0.022 (7.5 mg); p = 0.118 (12.5 mg) |
| Second-line | |||||||||
| N0626 [63] | Phase II | NSCLC | 100 | Sor+Pem | Pem | 3.4 vs 4.1m | 9.4 vs 9.1m | PFS; p = 0.22 | |
| CALGB30704 [64] | Phase II | NSCLC | 130 | Pem+Sun | Pem; Sun | 3.7 vs 4.9 vs 3.3 m (Sun alone) | 6.7 vs 10.5 vs 8.0 m (Sun alone) | 22% vs 17% vs 14 (Sun alone) | PFS; p = 0.25 |
| LUME-lung 1 [65] | Phase III | NSCLC | 1,311 | Doc+Nin | Doc | 3.4 vs 2.7 m | 10.0 vs 9.1 m | 4.4% vs 3.3% | PFS; p = 0.0019 |
| LUME-lung 2 [66] | Phase III | nsNSCLC | 713 | Pac+Nin | Pac | 4.4 vs 3.6 m | 12.0 vs 12.7 m | 9.1% vs 8.3% | PFS; p = 0.0435 |
| ZODIAC [65] | Phase III | NSCLC | 1,391 | Doc+Van | Doc | 4.0 vs 3.2 m | 10.6 vs 10.0 m | 17% vs 10% | PFS; p < 0.0001 |
| ZEAL [66] | Phase III | nsNSCLC | 534 | Pem+Van | Pem | 17.6 vs 11.9 w | 10.5 vs 9.2 m | 19% vs 8% | PFS; p = 0.108 |
NSCLC: non-small cell lung cancer; nsNSCLC: non-squamous non-small cell lung cancer; mPFS: median progression-free survival; mTTP: median time to progression; ORR: objective response rate; DCR: disease control rate; PE: Primary endpoint; Pac: paclitaxel; Car: carboplatin; Bev: bevacizumab; Ram: ramucirumab; Cis: cisplatin; Pla: platinum; Doc: docetaxel; Plac: placebo; Sor: Sorafenib; Mot; Motesanibb; Ced: cediranib; Van: Vandetanib; Paz: pazopanib; Axi: axitinib;; Lin: Linifanib; Sun: sunitinib; Nin: nintedanib; Erl: erlotinib; Lin: linifanib