Table 1. Trials evaluating bevacizumab or ramucirumab in combination with chemotherapy in locally advanced or metastatic NSCLC.
| Study | Design | Patients | n | Study arm | Control arm | mPFS/mTTP | mOS | ORR | PE, P value |
|---|---|---|---|---|---|---|---|---|---|
| First-line | |||||||||
| Johnson et al. [18] | Phase II | NSCLC | 99 | Pac+Car+Bev | Pac+Car | 7.4 (7.5 mg/kg) vs 4.3 (15 mg/kg) vs 4.2 m | 17.7 (7.5 mg/kg) vs 11.6 (15 mg/kg) vs 14.9 m | 31.5% (7.5 mg/kg) vs 28.1% (15 mg/kg) vs 18.8% | TTP; p = 0.023 (15 mg/kg) |
| ECOG 4599 [19] | Phase III | nsNSCLC | 878 | Pac+Car+Bev | Pac+Car | 6.2 vs 4.5 m | 12.3 vs 10.3 m | 35% vs 15% | OS; p = 0.003 |
| AVAIL [20, 21] | Phase III | nsNSCLC | 1,043 | Gem+Cis+Bev | Gem+Cis | 6.7 (7.5 mg/kg) vs 6.5 (15 mg/kg) vs 6.1 m | 13.6 (7.5 mg/kg) vs 13.4 (15 mg/kg) vs 13.1 m | 34.1% (7.5 mg/kg) vs 30.5% (15 mg/kg) vs 20.1% | PFS; p = 0.0003 (7.5 mg/kg), P = 0.0154 (15 mg/kg) |
| BEYOND [23] | Phase III | nsNSCLC | 276 | Pac+Car+Bev | Pac+Car | 9.2 vs 6.5 m | 24.3 vs 17.7 m | 54.4 vs 23.3% | OS; p = 0.0154 |
| JO19907 [22] | Phase II | nsNSCLC | 180 | Pac+Car+Bev | Pac+Car | 6.9 vs 5.9 m | 22.8 vs 23.4 m | 60.7% vs 31% | PFS; p = 0.009 |
| SAiL [24–26] | Phase IV | nsNSCLC | 2,212 | Patinum-based chemotherapy+Bev | 7.8 m | 14.6 m | 51% | ||
| Camidge et al. [41] | Phase II | NSCLC | 22 | Pal+Car+Ram | 7.85 m | 16.85 m | 55% | 6-month PFS: 59% | |
| Doebele et al. [42] | Phase II | nsNSCLC | 140 | Pem+Pla+Ram | Pem+Pla | 7.2 vs 5.6 m | 13.9 vs 10.4 m | 49.3% vs 38.0% | PFS; p = 0.132 |
| Maintenance | |||||||||
| Leon et al. [30] | Phase II | nsNSCLC | 49 | Vin+Cis+Bev→Bev | 6 m | 14.7 m | 29% | PFS | |
| Stevenson et al. [31] | Phase II | nsNSCLC | 43 | Pem+Car+Bev→Bev | 7.1 m | 17.1 m | 47% | PFS | |
| Patel et al. [32] | Phase II | nsNSCLC | 50 | Pem+Car+Bev→Pem+Bev | 7.8 m | 14.1 m | 55% | PFS | |
| AVAPERL [33, 34] | Phase III | nsNSCLC | 376 | Pem+cis+Bev→Pem+Bev | Pem+cis+Bev→Bev | 7.4 vs 3.7 m | 17.1 vs 13.2 m | 55.5% vs 50.0% | PFS; p < 0.0001 |
| POINTBREAK [35] | Phase III | nsNSCLC | 939 | Pem+Car+Bev→Pem+Bev | Pac+Car+Bev→Bev | 6.0 vs 5.6 m | 13.4 vs 12.6 m | 34.1% vs 33.0% | OS; p = 0.949 |
| PRONOUNCE [36] | Phase III | nsNSCLC | 371 | Pac+Car+Bev→Bev | Pem+Car→Pem | 3.91 vs 2.86 m | 11.7 vs 10.5 m | 23.6% vs 27.4% | G4PFS, p = 0.176 |
| Second-line | |||||||||
| Herbst et al. [37] | Phase II | nsNSCLC | 81 | Doc/Pem+Bev | Doc/Pem+Bev+Plac | 4.8 vs 3.0 m | 12.6 vs 8.6 m | 12.5% vs 12.2% | PFS; HR: 0.38 (95%CI: 0.38-1.16) |
| REVEL [43] | Phase III | NSCLC | 1,253 | Doc+Ram | Doc+Plac | 4.5 vs 3.0 m | 10.5 vs 9.1 m | 23% vs 14% | OS; p = 0.023 |
| Yoh [44] | Phase II | NSCLC | 197 | Doc+Ram | Doc+Plac | 5.22 vs 4.21 m | 15.15 vs 14.65 m | 28.9% vs 18.5% | PFS; 0.83 (0.59-1.16) |
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; PE: Primary endpoint; Pac: paclitaxel; Car: carboplatin; Bev: bevacizumab; Ram: ramucirumab; Gem: Gemcitabine; Cis: cisplatin; Pla: platinum; Doc: docetaxel; Plac: placebo; G4PFS: PFS without grade 4 toxicity; HR: hazard ratio