| Study [ref.] | Patients treated with TKI n | PFS | ORR % | Overall survival | Incidence of grade 3-5 adverse events# >1% of patients | Rate of discontinuation due to adverse events %¶ |
| NEJ002 [12, 23] | 114 | 10.8 months versus 5.4 months; HR 0.32 (95% CI 0.24–0.44), p<0.001 | 74 versus 31; p<0.001 | 27.7 months versus 26.6 months; HR 0.89 (95% CI 0.63–1.24), p = 0.483 | AST/ALT elevation 25%, rash 5.3%, appetite loss 5.3%, fatigue 2.6%, pneumonitis 2.6% | Not reported |
| WJTOG3405 [13, 25] | 51 for PFS (stage IIIb/IV subgroup) 86 for overall survival | 8.4 months versus 5.3 months; HR 0.33 (95% CI 0.21–0.54), p<0.0001 (stage IIIb/IV subgroup) | 62 versus 32++; p<0.0001 | 36 months versus 39 months; HR 1.19 (95% CI 0.771.83), p = 0.443 | Whole population (including those with recurrent disease): ALT elevations 27.6%, AST elevations 16.1%, fatigue 2.3%, rash 2.3%, diarrhoea 1.1%, paronychia 1.1%, nausea 1.1%, sensory disturbance 1.0% | 16 |
| IPASS+ [8, 14] | 132 | 9.5 months versus 6.3 months; HR 0.48 (95% CI 0.36–0.64), p<0.001 | 71 versus 47; p<0.001 | 21.6 months versus 21.9 months; HR 1.00 (95% CI 0.76–1.33), p = 0.990) | Whole population: diarrhoea 3.8%, neutropenia 3.7%, rash or acne 3.1%, anaemia 2.2%, anorexia 1.5%, leukopenia 1.5% | Whole population, 7 |
| EURTAC§ [9, 19] | 86 | 9.7 months versus 5.2 months; HR 0.37 (95% CI 0.25–0.54), p<0.0001 | 58 versus 15; p-value not reported | 19.3 months versus 19.5 months; HR 1.04 (95% CI 0.65–1.68), p = 0.87 | Rash 13%, fatigue 6%, diarrhoea 5%, AST/ALT 2%, anaemia 1%, neuropathy 1%, arthralgia 1%, pneumonitis 1% | 13 |
| EURTAC,ƒ [9, 19] | 86 | 10.4 months versus 5.4 months; HR 0.47 (95% CI 0.28–0.78), p = 0.0030 | ||||
| LUX-Lung 3## | 230 | 11.1 months versus 6.9 months; HR 0.58 (95% CI 0.43–0.78); p = 0.001 | 56 versus 23; p = 0.001 | 28.1 months versus 28.2 months; HR 0.91 (95% CI 0.66–1.25), p = 0.55 (yet immature) | Rash/acne 16.2%, diarrhoea 14.4%, paronychia 11.4%, stomatitis/mucositis 8.7%, decreased appetite 3.1%, vomiting 3.1%, fatigue 1.3% | 8 |
| LUX-Lung 3§ [15] | 230 | 11.1 months versus 6.7 months; HR 0.49 (95% CI 0.37–0.65); p = 0.001 | 69 versus 44; p = 0.001 | |||
| OPTIMAL [10, 11] | 82 | 13.1 months versus 4.6 months; HR 0.16 (95% CI 0.10–0.26), p<0·0001 | 83 versus 36; p<0.0001 | 22.7 months versus 28.9 months; HR 1.04 (95% CI 0.69–1.58), p = 0.69 (yet immature) | ALT 4%, rash 2% | 1 |
| LUX-Lung 6¶¶ [16] | 242 | 11.0 months versus 5.6 months; HR 0.28 (95% CI 0.20–0.39), p<0.0001 | 67 versus 23; p<0.0001 | Not reported; immature | Rash/acne 14.6%, diarrhoea 5.4%, stomatitis/mucositis 5.4%, ALT increase 1.7%, decreased appetite 1.3% | 6 |
| LUX-Lung 6§ [16] | 242 | 13.7 months versus 5.6 months; HR 0.26 (95% CI 0.19–0.36), p<0.0001 | 74 versus 31; p-value not reported | |||
| ENSURE¶¶ [17] | 110 | 11.0 months versus 5.6 months; HR 0.42 (95% CI 0.27–0.66), p<0.0001 | 63 versus 34; p = 0.0001 | Not reported; immature | Rash 6.4%, diarrhoea 1.8%§§ | 3 |
| ENSURE§ [17] | 110 | 11.0 months versus 5.5 months; HR 0.34 (95% CI 0.22–0.51), p<0.0001) |
NEJ002: North East Japan 002; WJTOG: West Japan Thoracic Oncology Group; IPASS: Iressa Pan-Asia Study; EURTAC: European Randomised Trial of Tarceva versus Chemotherapy; PFS: progression-free survival; ORR: overall response rate; HR: hazard ratio; ALT: alanine transaminase; AST: aspartate aminotransferase. #: TKI treatment only; ¶: TKI treatment only, independent of relation to study drug; +: mutation-positive subgroup; §: investigator assessed; ƒ: investigator assessment based on 45 patients, independent review based on 31 patients treated with erlotinib; ##: independent review (primary end-point); ¶¶: independent assessed; ++: measurable disease but stage-independent (TKI and chemotherapy combined n = 117); §§: only adverse events of special interest were reported.