Table 1. Recent Phase III Trials combining chemotherapy and targeted agents in the past two years.
| Targeted agent | Trial design and chemo partner | Sequencing of targeted agent | N | Outcome |
|---|---|---|---|---|
| EGFR inhibitors Erlotinib FAST-ACT2 (22) | First line, unselected platinum/gemcitabine + erlotinib or placebo on days 15-28 f/by erlotinib or placebo | Intercalated + maintenance | 451 | PFS =7.6 vs. 6.0 months, HR =0.57 (0.47-0.69) P<0.0001; OS =18.3 vs. 15.2 months, HR =0.79 (0.64-0.99) P=0.0420; intercalated erlotinib vs. placebo |
| Cetuximab SELECT (23) | Second line, squamous Pem/cetux vs. Pem vs. docetaxel/cetux vs. docetaxel f/by cetux in cetux arms | Concurrent + maintenance | Pem =605; | PFS =2.70 vs. 2.27 months, HR =0.93 (0.81-1.08) P=0.305; OS =6.74 vs. 7.85 months HR 1.05, (0.91-1.2) P=0.47; cetux + chemo vs. chemo |
| Docetaxel =333 | ||||
| VEGF Bevacizumab PRONOUNCE (24) | First line, non squamous PemC vs. PCB f/by Pem (PemC Arm) or Bev (PCBArm) | Concurrent + maintenance | 361 | PFS =4.4 vs. 5.5months, HR =1.06 (0.84-1.35) P=0.610; |
| OS =10.5 vs. 11.7 months HR =1.07 (0.83-1.36) P=0.616; PemC vs. PCB | ||||
| Bevacizumab PointBreak (25) | First line, non squamous PemCB f/by Pem+Bev vs. PCB f/by Bev | Concurrent + maintenance | 939 | PFS =6 vs. 5.6 months, HR =0.83 (0.71-0.9) P=0.012; OS =12.6 vs. 13.4 months HR =1.00 (0.86-1.16) P=0.943; PemCB vs. PCB |
| Cediranib NCIC BR29 (26) | First line, unselected Carbo/taxol + CED or placebo f/by CED or placebo | Concurrent + maintenance | 306 | PFS= 5.5 vs. 5.5 months, HR =0.91 (0.71-1.18); OS =12.2 vs. 12.1 months, HR =0.95 (0.69-1.30) P=0.74; |
| CED vs. placebo | ||||
| Sorafenib NExUS (27) | First line, Non squamous cis/gem plus sorafenib or placebo f/by sorafenib or placebo | Concurrent + maintenance | 772 | PFS = 6.0 vs. 5.5 months, HR =0.83 (0.71-0.97) P=0.008; |
| OS = 12.4 vs. 12.5 months, HR =0.98 (0.83-1.16) P=0.40; sorafenib vs. placebo | ||||
| Aflibercept VITAL (28) | Second line, non-squamous Docetaxel + Aflibercept or placebo | Concurrent | 913 | PFS =5.2 vs. 4.1 months, HR =0.82 (0.72-0.94) P=0.820; |
| OS =10.1 vs. 10.4 months, HR =1.01 (0.87-1.17) P=0.9; aflibercept vs. placebo | ||||
| Multitargeted agents Nintedanib (VEGFR, FGFR,PDGFR inhibitor) LUME-lung2 (29) | Second line, non-squamous PEM + Nintedanib or Placebo | Concurrent | 713 | PFS =4.4 vs. 3.6 months, HR =0.83 (0.7-0.99) P=0.04; |
| OS = No difference in OS, HR =1.03; nintedanib vs. placebo | ||||
| Nintedanib LUME-lung1 (30) | Second line Docetaxel + Nintedanib or Placebo | Concurrent | 1,314 | PFS =3.4 vs. 2.7 months, HR =0.79 (0.68-0.92) P=0.0019; OS in all pts 10.1 vs. 9.1 months HR =0.94 P=0.272; nintedanib vs. placebo |
| Vandetanib (31) (VEGF, EGFR inhibitor) | Second line PEM + Vandetanib or Placebo | Concurrent | 534 | PFS =17.6 vs. 11.9 weeks, HR =0.86 (0.69 to 1.06) P=0.108; |
| OS =10.5 vs. 9.2 months, HR, 0.86 (0.65-1.13) P=0.219; vandetanib vs. placebo |
Pem/cetux, Pemetrexed/cetuximab; Pem, Pemetrexed; docetaxel/cetux, docetaxel/cetuximab; PemCB, Pem/Carbo/Bev; CED, Cedirinib; PCB, Paclitaxel/Carboplatin/Bevacizumab; PemC, Pemetrexed/Carboplatin; Carbo/taxol, Carboplatin/paclitaxel.