Table 2.
Relevant second- and third-line phase III trials
| Trial | Comparison | Population characteristics | Efficacy in all patients | Efficacy in subgroup enriched for EGFR wt | Mutational analysis | Efficacy by mutational status |
| BR.21[1,21] | E (n = 488) vs P (n = 243) | Second line (51%) or third line (49%); nonADC, 50%; non-Asian, 87% | OS for E, 6.7 mo; OS for P, 4.7 mo; HR 0.70; P < 0.001 | NonADC HR, 0.8; non-Asian HR, 0.8 | n = 204 (27.9%); EGFR activating mutation, 34 | EGFR mutated: OS HR, 0.55; EGFR wt OS HR, 0.74; interaction P = 0.47 |
| ISEL[20,23] | G (n = 959) vs P (n = 480) | Second line (49%) or third line (51%); nonADC 52%; non-Asian, 90% | OS for G, 5.6 mo; OS for P, 5.1 mo; HR, 0.89; P = 0.089 | NonADC HR < 1.01; non-Asian HR = 0.92 | n = 215 (14.9%); activating EGFR mutation, 26 | NR |
| INTEREST[24,25] | G (n = 723) vs D (n = 710) | Second line (84%) or third line (16%); nonADC, 44%; non-Asian, 78% | OS for G, 7.6 mo; OS for D, 8 mo; HR, 1.02 (met non inferiority criteria) | NonADC HR < 11; non-Asian HR = 11 | n = 297 (20.7%); activating EGFR mutation, 44 | EGFR mutated: OS HR, 0.83; EGFR wt: OS HR, 1.02; interaction P = 0.59 |
| TITAN[26] | E (n = 203) vs D/Pem (n = 221) | Second line; non-Asian, 86%; nonADC, 55% | OS for E, 5.3 mo; OS for D/Pem, 5.5 mo; HR = 0.96; P = 0.73 | Squamous OS HR = 0.86; non-Asian OS HR = 0.94 | n = 167 (39.3%); activating EGFR mutation, 18 | EGFR mutated: OS HR = 1.19; EGFR wt: OS HR = 0.85 |
| HORG[27] | E (n = 166) vs Pem (n = 166) | Second line (57%) or third line (43%); nonADC, 77.5%; non-Asian, 100% | PFS for E, 3.6 mo; PFS for Pem 2.9 mo; P = 0.136; OS for E, 8.2 mo; OS for Pem, 10.1 mo; P = 0.986 | Squamous OS HR = 1.97 | n = 123 (37%); activating EGFR mutations, 11 | NR |
1
HR estimated from forest plot in publication. ADC: Adenocarcinoma; C: Cisplatin; Cb: Carboplatin; D: Docetaxel; E: Erlotinib; EGFR: Epidermal growth factor receptor; G: Gefitinib; Gem: Gemcitabine; HR: Hazard ratio; NR: Not reported; OS: Median overall survival; P: Placebo; Pem: Pemetrexed; PFS: Median progression free survival; T: Paclitaxel; wt: Wild type.