Table 1. Recent phase III trials assessing antiangiogenic agents in a first-line setting
Agent and study name [ref.]Target (s)Study designOverall response rateProgression-free survivalOverall survival
Monoclonal antibodies
    Bevacizumab; ECOG 4599 [14]VEGFStage IIIB/IV non-squamous NSCLC Patients randomised to: carboplatin/paclitaxel (n = 444) or carboplatin/paclitaxel + bevacizumab (15 mg·kg−1; n = 434) Primary end-point: overall survivalCarboplatin/paclitaxel: 15% Carboplatin/paclitaxel + bevacizumab: 35% (p<0.001)Carboplatin/paclitaxel: 4.5 months Carboplatin/paclitaxel + bevacizumab: 6.2 months HR 0.66 (95% CI 0.57–0.77); p<0.001Carboplatin/paclitaxel: 10.3 months Carboplatin/paclitaxel + bevacizumab: 12.3 months HR 0.79 (95% CI 0.67–0.92); p = 0.003
    Bevacizumab; AVAiL [21, 22]VEGFStage IIIB/IV non-squamous NSCLC Patients randomised to: cisplatin/gemcitabine (n = 347), cisplatin/gemcitabine + bevacizumab (7.5 mg·kg−1; n = 345) or cisplatin/gemcitabine + bevacizumab (15 mg·kg−1; n = 351) Primary end-point: progression-free survivalCisplatin/gemcitabine: 20.1% Cisplatin/gemcitabine + bevacizumab (7.5 mg·kg−1): 34.1% Cisplatin/gemcitabine + bevacizumab (15 mg·kg−1): 30.4% (p<0.0001 and p = 0.0023, respectively)Cisplatin/gemcitabine: 6.1 months Cisplatin/gemcitabine + bevacizumab (7.5 mg·kg−1): 6.7 months Cisplatin/gemcitabine + bevacizumab (15 mg·kg−1): 6.5 months HR 0.75 (95% CI 0.62–0.91); p = 0.003 and HR 0.92 (95% CI 0.68–0.98); p = 0.03, respectivelyCisplatin/gemcitabine: 13.1 months Cisplatin/gemcitabine + bevacizumab (7.5 mg·kg−1): 13.6 months Cisplatin/gemcitabine + bevacizumab (15 mg·kg−1): 13.4 months HR 0.92 (95% CI 0.78–1.11); p = 0.420 and HR 1.03 (95% CI 0.86–1.23); p = 0.761, respectively
Multi-targeted antiangiogenic orally administered TKIs
    Cediranib; BR24 [23]VEGFR-1–3, PDGFR-β, FGFR-1 and c-kitStage IIIB/IV NSCLC all histologies Patients randomised to: carboplatin/paclitaxel (n = 125) or carboplatin/paclitaxel + cediranib (30 mg·day−1; n = 126) Primary end-point: progression-free survivalCarboplatin/paclitaxel: 16% Carboplatin/paclitaxel + cediranib: 38% (p<0.0001)Carboplatin/paclitaxel: 5.0 months Carboplatin/paclitaxel + cediranib: 5.6 months HR 0.77 (95% CI 0.56–1.08); p = 0.13Carboplatin/paclitaxel: 10.1 months Carboplatin/paclitaxel + cediranib: 10.5 months HR 0.78 (95% CI 0.57–1.06); p = 0.11
    Cediranib; BR29 [24]VEGFR-1–3, PDGFR-β, FGFR-1 and c-kitStage IIIB/IV NSCLC all histologies Patients randomised to: carboplatin/paclitaxel or carboplatin/paclitaxel + cediranib (20 mg·day−1) Primary end-point: overall survivalCarboplatin/paclitaxel: 34% Carboplatin/paclitaxel + cediranib: 52% (p = 0.001)Carboplatin/paclitaxel: 5.5 months Carboplatin/paclitaxel + cediranib: 5.5 months HR 0.91 (95% CI 0.71–1.18); p = 0.5Carboplatin/paclitaxel: 12.1 months Carboplatin/paclitaxel + cediranib: 12.2 months HR 0.95 (95% CI 0.69–1.30); p = 0.74
    Sorafenib; ESCAPE [25]VEGFR-2–3, PDGFR-β, c-kit, Raf and flt-3Stage IIIB/IV NSCLC all histologies Patients randomised to: carboplatin/paclitaxel (n = 462) or carboplatin/paclitaxel + sorafenib (400 mg; n = 464) Primary end-point: overall survivalCarboplatin/paclitaxel: 27% Carboplatin/paclitaxel + sorafenib: 24% (p = 0.102)Carboplatin/paclitaxel: 5.4 months Carboplatin/paclitaxel + sorafenib: 4.6 months HR 0.99 (95% CI 0.84–1.16); p = 0.433Carboplatin/paclitaxel: 10.6 months Carboplatin/paclitaxel + sorafenib: 10.7 months HR 1.15 (95% CI 0.94–1.41); p = 0.915
    Sorafenib; NExUS [26]VEGFR-2–3, PDGFR-β, c-kit, Raf and flt-3Stage IIIB/IV non-squamous NSCLC Patients randomised to: gemcitabine/cisplatin (n = 387) or gemcitabine/cisplatin + sorafenib (400 mg; n = 385) Primary end-point: overall survivalGemcitabine/cisplatin: 26% Gemcitabine/cisplatin + sorafenib: 28% (p = 0.27)Gemcitabine/cisplatin: 5.5 months Gemcitabine/cisplatin + sorafenib: 6.0 months HR 0.83 (95% CI 0.71–0.97); p = 0.008Gemcitabine/cisplatin: 12.5 months Gemcitabine/cisplatin + sorafenib: 12.4 months HR 0.98 (65% CI 0.83–1.16); p = 0.401
    Motesanib; MONET1 [27]VEGFR-1–3, PDGFR-β, c-kit and RETStage IIIB/IV non-squamous NSCLC Patients randomised to: carboplatin/paclitaxel (n = 549) or carboplatin/paclitaxel + motesanib (125 mg; n = 541) Primary end-point: overall survivalCarboplatin/paclitaxel: 26% Carboplatin/paclitaxel + motesanib: 40% (p<0.001)Carboplatin/paclitaxel: 5.4 months Carboplatin/paclitaxel + motesanib: 5.6 months HR 0.79 (95% CI 0.61–0.98); p<0.001Carboplatin/paclitaxel: 11.0 months Carboplatin/paclitaxel + motesanib: 13.0 months HR 0.90 (95% CI 0.78–1.04); p = 0.14
Vascular disrupting agents
    Vadimezan; ATTRACT-1 [28]Stage IIIB/IV NSCLC all histologies Patients randomised to: carboplatin/paclitaxel (n = 650) or carboplatin/paclitaxel + vadimezan (1800 mg·m−2; n = 649) Primary end-point: overall survivalCarboplatin/paclitaxel: 25% Carboplatin/paclitaxel + vadimezan: 25% (p = 1.0)Carboplatin/paclitaxel: 5.5 months Carboplatin/paclitaxel + vadimezan: 5.5 months HR 1.04 (95% CI 0.91–1.19); p = 0.727Carboplatin/paclitaxel: 12.7 months Carboplatin/paclitaxel + vadimezan: 13.4 months HR 1.01 (95% CI 0.85–1.19); p = 0.535
  • ECOG: Eastern Cooperative Oncology Group; AVAiL: Avastin in Lung Cancer; TKI: tyrosine kinase inhibitor; ESCAPE: Evaluation of Sorafenib, Carboplatin and Paclitaxel Efficacy in NSCLC; NExUS: NSCLC research Experience Utilising Sorafenib; MONET1: Motesanib NSCLC Efficacy and Tolerability Study; ATTRACT-1: Antivascular Targeted Therapy: Researching ASA404 in Cancer Treatment; VEGF: vascular endothelial growth factor; VEGFR: VEGF receptor; PDGFR: platelet-derived growth factor receptor; FGFR: fibroblast growth factor receptor; RET: Rearranged during Transfection; NSCLC: nonsmall cell lung cancer; HR: hazard ratio.