Table 1. Phase III Trials comparing EGFR-inhibitors to chemotherapy in advanced stage IIIB/IV NSCLC.
| Trial [year] (Ref) | Patient selection | Targeted therapy (TT) | Comparator (C) | Median PFS TT vs. C (mo.) | HR | P value |
|---|---|---|---|---|---|---|
| First-line EGFR TKI versus chemotherapy | ||||||
| IPASS [2009] (39,40) | n=1,217, clinical, non/light smokers, Adc, 60% EGFR mutant (Asia) | Gefitinib | Carboplatin; Paclitaxel | 9.8 vs. 6.4 | 0.48 | ≤0.001 |
| First-SIGNAL [2012] (41) | n=309, clinical, never smokers, Adc, 44% EGFR mutant | Gefitinib | Cisplatin; Gemcitabine | 5.8 vs. 6.4 | 1.198 | 0.138 |
| WJTOG3405 [2010] (42) | n=172, molecular EGFR mutant | Gefitinib | Cisplatin; Docetaxel | 9.2 vs. 6.3 | 0.489 | <0.0001 |
| NEJSG [2010] (43) | n=230, molecular EGFR mutant | Gefitinib | Carboplatin; Paclitaxel | 10.8 vs. 5.4 | 0.3 | <0.001 |
| OPTIMAL [2011] (44) | n=154, molecular EGFR mutant, 88% Adc | Erlotinib | Carboplatin; Gemcitabine | 13.1 vs. 4.6 | 0.16 | <0.0001 |
| EURTAC [2012] (45) | n=174, molecular EGFR mutant | Erlotinib | Platinum doublet | 9.7 vs. 5.2 | 0.37 | <0.0001 |
| LUX-Lung3 [2013] (46) | n=345, molecular EGFR mutant Adc | Afatinib | Cisplatin; Pemetrexed | 11.1 vs. 6.9 | 0.58 | 0.001 |
| LUX-Lung6 [2014] (47) | n=364, molecular EGFR mutant Adc | Afatinib | Cisplatin; Gemcitabine | 11.0 vs. 5.6 | 0.28 | <0.0001 |
| First-line EGFR therapy plus chemotherapy | ||||||
| INTACT-1 [2004] (48) | n=1,093, unselected, Adc + SCC | Gefitinib 500 mg/250 mg or placebo + chemotherapy | Cisplatin + Gemcitabine (chemotherapy alone) | 5.5 (500 mg), 5.8 (250 mg) vs. 6.0 | NR | 0.7633 |
| INTACT-2 [2004] (49) | n=1,037, unselected, Adc + SCC | Gefitinib 500 mg/250 mg or placebo + chemotherapy | Carboplatin + Paclitaxel (chemotherapy alone) | 4.6 (500 mg), 5.3 (250 mg) vs. 5.0 | NR | 0.0562 |
| TRIBUTE [2005] (50) | n=1,059, unselected, Adc + SCC | Erlotinib + chemotherapy then maintenance Erlotinib | Carboplatin; Paclitaxel | 5.1 vs. 4.9 | 0.937 | 0.36 |
| TALENT [2007] (51) | n=1,172, unselected, Adc + SCC | Erlotinib + chemotherapy | Cisplatin; Gemcitabine | 5.5 vs. 5.7 (23.7 vs. 24.6 wks.) | 0.98 | 0.74 |
| FLEX [2009] (52) | n=1,125, Adc + SCC, EGFR expression | Cetuximab + chemotherapy | Cisplatin; Vinorelbine | 4.8 vs. 4.8 | 0.943 | 0.39 |
| BMS099 [2010] (53) | n=676, unselected, Adc + SCC | Cetuximab + chemotherapy | Carboplatin; Paclitaxel or Docetaxel | 4.40 vs. 4.24 | 0.902 | 0.2358 |
| TORCH [2012] (54, 55) | n=760, unselected, Adc + SCC | Erlotinib (followed by Cisplatin Gemcitabine) | Cisplatin Gemcitabine (followed by Erlotinib) | 6.4 vs. 8.9 | 1.21 | NR |
| Second- or third-line EGFR TKI versus placebo | ||||||
| BR.21 [2005] (56) | n=731, unselected, Adc + SCC | Erlotinib | Placebo | 2.2 vs. 1.8 (OS 6.7 vs. 4.7, P<0.001) | 0.61 | <0.001 |
| ISEL [2005] (57) | n=1,692, unselected, Adc + SCC | Gefitinib | Placebo | 3.0 vs. 2.6 | 0.82 | 0.0006 |
| Second or third-line EGFR TKI versus chemotherapy | ||||||
| INTEREST [2008] (31) | n=1,433, unselected, Adc + SCC, EGFR mutant subgroup | Gefitinib | Docetaxel | 2.2 vs. 2.7 | 1.04 | 0.47 |
| V-15-32 [2008] (32) | n=489, unselected, Adc + SCC | Gefitinib | Docetaxel | 2.0 vs. 2.0 | 0.9 | 0.335 |
| ISTANA [2010] (33) | n=161, unselected, Adc + SCC | Gefitinib | Docetaxel | 3.3 vs. 3.4 (6 months PFS 32% vs. 13%) | 0.729 | 0.04 |
| TITAN [2012] (34) | n=424, unselected, Adc + SCC | Erlotinib | Docetaxel or Pemetrexed (physician’s choice) | 1.4 vs. 1.9 (6.3 vs. 8.6 wks.) | 1.19 | 0.089 |
| TAILOR [2013] (58) | n=222, molecular EGFR wild type, KRAS testing, Adc + SCC | Erlotinib | Docetaxel | 2.9 (Docetaxel) vs. 2.4 (Erlotinib) in EGFR wild type | 0.71 | 0.02 |
Adc, adenocarcinoma; SCC, squamous cell carcinoma; PFS, progression-free survival; HR, hazard ratio; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; mo, months; wks, weeks.