Table 1.

Characteristics of NSCLC studies of monotherapy TKI included in analyses

Somatic EGFR mutationsGene statusStudy treatmentEntry criteria/stageResponse criteriaEthnicityMethod of analysis
Patients, nMutations, n (%)Patients, nGene Gain, n (%)Somatic mutationGene copy number
Pao (2004)43*3523 (65.7)Gefitinib/erlotinibEAP + MRECISTWhiteSEQ
Bell (2005)357913 (16.5)867 (8.1)GefitinibEAP + III/IVRECISTMixedSEQQ-PCR ≥ 4
Chou (2005)445433 (61.1)GefitinibEAP + III/IVRECISTAsianSEQ
Cortez-Funes (2005)45§8310 (12.1)GefitinibEAP + MRECISTWhiteSEQ
Han (2005)46§9017 (18.9)GefitinibM + III/IVWHOAsianSEQ
Kim (2005)47§276 (22.2)GefitinibEAP + III/IVRECISTAsianSEQ
Kondo (2005)48§124 (33.3)GefitinibN + MRECISTAsianSEQ
Mu (2005)49§2210 (45.5)GefitinibEAP + MRECISTAsianSEQ
Takano (2005)50§6629 (43.9)GefitinibM + MRECISTAsianQ-PCR ≥ 3
Taron (2005)51§6817 (25.0)GefitinibEAP + III/IVRECISTMixedSEQ
Tomizawa (2005)52§2010 (50.0)GefitinibN + MNRAsianSEQ
Tsao (2005)53§9716 (16.5)ErlotinibEAP + III/IVRECISTMixedSEQ
Zhang (2005)54§3012 (40.0)GefitinibEAP + III/IVRECISTAsianSEQ
Endo (2006)55§224 (18.2)GefitinibN + MRECISTAsianQ-PCR ≥ 3
Endoh (2006)56§5227 (51.9)5226 (50.0)GefitinibN + MRECISTaAsianSEQQ-PCR ≥ 0.915 cut
Giaccone (2006)57§297 (24.1)ErlotinibN + III/IVRECISTWhiteSEQ
Han (2006)58§6631 (47.0)GefitinibM + III/IVRECISTAsianCCS
Hirsch (2006)59§13216 (12.1)22267 (30.2)GefitinibEAP + III/IVRECISTMixedHSCCS
Hsieh (2006)60§6532 (49.2)GefitinibM + III/IVRECISTAsianHS
Hung (2006)61§115 (45.5)GefitinibM + III/IVRECISTAsianSEQ
Jannë (2006)62§229 (40.9)GefitinibM + MWHOWhiteHS
Kimura (2006)63§2713 (48.1)GefitinibN + III/IVRECISTAsianHS
Koyama (2006)64§3416 (47.1)GefitinibM + MRECISTAsianSEQ
Niho (2006)65§134 (30.8)GefitinibN + III/IVRECISTAsianSEQ
Oshita (2006)66§2511 (44.0)GefitinibEAP + III/IVNRAsianHS
Shih (2006)67§6229 (46.8)GefitinibM + III/IVRECISTAsianSEQ
Uramoto (2006)68§209 (45.0)GefitinibM + MRECISTaAsianSEQ
Buckingham (2007)69§5617 (30.4)GefitinibEAP + III/IVRECISTWhiteSEQ
Cappuzzo (2007)23*3624 (66.7)3625 (69.4)GefitinibEAP + III/IVRECISTWhiteHSCCS
Hirsch (2007)70*15843 (27.2)18359 (32.2)GefitinibM + III/IVRECISTWhiteSEQCCS
Ichihara (2007)71§838 (38.8)GefitinibEAP + III/IVWHOAsianSEQ
Jackman (2007)72§439 (20.9)ErlotinibN + III/IVRECISTWhiteSEQ
Kimura (2007)73§429 (21.4)GefitinibM + III/IVRECISTAsianHS
Loprevite (2007)74§215 (23.8)187 (38.9)GefitinibEAP + III/IVRECISTWhiteSEQCCS
Massarelli (2007)75§717 (9.9)5932 (45.2)Gefitinib/erlotinibEAP + III/IVRECISTWhiteSEQCCS
Okami (2007)76§4625 (54.3)GefitinibN + MRECISTAsianSEQ
Pallis (2007)77§8625 (29.1)GefitinibEAP + III/IVWHOWhiteSEQ
Pugh (2007)78§358 (22.9)247 (29.2)GefitinibEAP + III/IVWHOMixedSEQCCS
Satouchi (2007)79§9128 (30.8)GefitinibM + MRECISTAsianHS
Sequist (2007)80*5928 (47.5)Gefitinib/erlotinibM + MRECISTWhiteSEQ
Shoji (2007)81*3019 (63.3)GefitinibM + MRECISTaAsianSEQ
Soh (2007)82§7230 (41.7)GefitinibEAP + III/IVRECISTAsianCCS
Sone (2007)83§5917 (28.8)5426 (48.2)GefitinibM + III/IVRECISTAsianSEQCCS
Takano (2007)84§20784 (41.1)GefitinibM + MRECISTAsianHS
Van Zandwijk (2007)85§153 (20.0)GefitinibEAP + III/IVRECISTWhiteSEQ
Weiss (2007)86§5828 (48.3)GefitinibM + MRECISTAsianHS
Zhang (2007)87§2415 (62.5)GefitinibM + MNRAsianSEQ
Ahn (2008)88§9224 (26.1)8836 (40.9)ErlotinibEAP + III/IVRECISTAsianSEQQ-PCR ≥ 3
Chang (2008)89§3622 (61.1)Gefitinib/erlotinibM + III/IVRECISTAsianCISH ≥ 5
Chen (2008)90*1512 (80.0)GefitinibEAP + NRNRAsianSEQ
Dongiavanni (2008)91§439 (20.9)4314 (32.6)GefitinibEAP + III/IVRECISTWhiteSEQFISH ratio > 2.2
Ebi (2008)92§177 (41.2)GefitinibEAP + III/IVRECISTAsianHS
Felip (2008)93§354 (11.4)5715 (26.3)ErlotinibEAP + MRECISTWhiteSEQCCS
Hijiya (2008)94§2111 (52.4)GefitinibN + MRECISTAsianSEQ
Kawada (2008)95§3618 (50.0)GefitinibNR + MRECISTAsianHS
Maheswaran (2008)96*1813 (72.2)Gefitinib/erlotinibM + MRECISTWhiteHS
Miller (2008)97*8118 (22.2)7624 (31.6)ErlotinibM + III/IVRECISTWhiteSEQCISH ≥ 4
Miyanaga (2008)98§2410 (41.7)GefitinibM + MRECISTAsianHS
Sasaki (2008)99§2715 (55.6)2712 (44.4)GefitinibM + MRECISTAsianHSCCS
Schneider (2008)34§724 (5.6)16141 (25.5)ErlotinibEAP + III/IVRECISTWhiteSEQCCS
Xu (2008)100§7432 (43.2)GefitinibEAP + III/IVRECISTAsianSEQ
Yamanaka (2008)101§189 (50.0)GefitinibNRNRAsianSEQ
Yang (2008)102§8152 (64.2)GefitinibN + III/IVRECISTAsianSEQ
Zhu (2008)103§9128 (30.8)ErlotinibEAP + III/IVRECISTMixedCCS
Zucali (2008)104§4631 (67.4)GefitinibEAP + III/IVRECISTWhiteSEQ

NOTE: The numbers of patients analyzed for the presence of somatic EGFR mutations or EGFR gene copy number are indicated, as are the percentages of “positive” patients for each technique. References are supplied in the Supplementary References Table, numbered as Sn.

Abbreviations: Gefitinib/erlotinib, administration of either gefitinib or erlotinib to an ill-defined percentage of patients; EAP, expanded access program (or equivalent); M, mixed (stages I and above, OR naïve through to multiple lines of chemotherapy; mixed contingent of >10% of any population; where appropriate); III/IV, stage III and above, including advanced; Mixed, Asians and Whites, wherein one ethnicity was >10% of the population; this similarly applied to Treatment and Recruitment; N, naïve (chemotherapy); RECISTa, amended RECIST; SEQ, sequencing of any of the exons 18 to 21 of the gene (typically bidirectional); HS, higher sensitivity of mutational analysis (e.g., allelic discrimination; RFLP) compared with standard sequencing; CCS, according to the Colorado Classification System on the gene copy number status of EGFR in NSCLC (22); NR, not reported.

  • *Biased participant selection.

  • Nonsponsored study.

  • Company-sponsored study.

  • §Nonbiased participant selection