Copyright ©2013 Baishideng Publishing Group Co.
World J Clin Oncol. May 10, 2013; 4(2): 29-42
Published online May 10, 2013. doi: 10.5306/wjco.v4.i2.29
Table 1 Selected phase III and randomized phase II trials comparing epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy as first-line therapy in patients with advanced non-small cell lung cancer
TrialnType of studyStudy designOS (mo)P valuePFS (mo)P valueORR (%)P value
HR (95%CI)HR (95%CI)HR (95%CI)
Fukuoka et al[34]261RetrospectiveGefitinib vs PC21.6 vs 21.99.6 vs 6.371.2 vs 47.3
1.00 (0.76-1.33)0.990.48 (0.36-0.64)0.00012.75 (1.65-4.6)0.0001
Han et al[98]42RetrospectiveGefitinib vs Cis + G27.2 vs 25.68.0 vs 6.384.6 vs 37.5
1.04 (0.49-2.18)NA0.54 (0.26-1.1)0.0869.16 (2.10-39.84)0.002
Mitsudomi et al[99]172ProspectiveGefitinib vs Cis + D35.5 vs 38.89.6 vs 6.662.1 vs 32.1
1.18 (0.76-1.8)0.440.52 (0.37-0.71)0.0013.44 (1.60-7.37)0.0001
Maemondo et al[35], Inoue et al[100]228ProspectiveGefitinib vs PC27.7 vs 26.610.8 vs 5.473.7 vs 30.7
0.88 (0.63-1.24)0.480.32 (0.23-0.43)0.0016.32 (3.55-11.25)0.001
Chen et al[28]154ProspectiveErlotinib vs C + G22.7 vs 28.8513.7 vs 4.683 vs 36
1.04 (0.69-1.58)0.690.16 (0.10-0.26)0.0001NA0.0001
Rosell et al[29]173ProspectiveErlotinib vs platinum-based doublets19.3 vs 19.59.7 vs 5.2581vs 151
1.04 (0.65-1.68)0.870.37 (0.25-0.54)0.0001NANA
Yang et a2l[101]345ProspectiveAfatinib vs Cis + PNM11.13vs 6.9356.13vs 22.63
0.58 (0.43-0.78)0.0004NA0.001
Jänne et al[102]345ProspectiveErlotinib vs erlotinib + PC24.6 vs 19.85.0 vs 6.635 vs 46
Table 2 Phase III clinical trials testing antiangiogenic tyrosine kinase inhibitors in combination with chemotherapy in non-small cell lung cancer
TrialnStudy designPEOS (mo)PFS (mo)ORR (%)
Vandetanib second-line
ZEAL[103]534PV vs PPFS10.5 vs 9.217.6 wk vs 11.9 wk19 vs 8
ZEST[104]1240EV vs EPFS6.9 vs 7.82.6 vs 2.012 vs 12
ZODIAC[105]1391DV vs DPFS10.6 vs 10.04.0 vs 3.2NA
Vandetanib second or third-line
ZEPHYR[106]924V vs placeboOS8.5 vs 7.8NA2.6 vs 0.7
Sorafenib first-line
NEXUS[107]904G + Cis + S f/b S vs G + Cis f/b placeboOS376 d vs 379 d183 d vs 168 d28 vs 26
Motesanib first-line
MONET[6]1090PC + M vs PCOS13.0 vs 11.05.6 vs 5.440 vs 26
Cediranib first-line
BR29 (active, no longer recruiting, NCT00795340)750PC + Ced vs PCOSNANANA
Nintedanib second-line
LUME-Lung 1 (active, no longer recruiting, NCT00805194)1300D + Nin vs DPFSNANANA
LUME-Lung 2 (active, no longer recruiting, NCT00806819)1302P + Nin vs PPFSNANANA
Table 3 Major ongoing clinical trials with crizotinib for advanced non-small cell lung cancer1
Trial numberPhaseStudy designKey entry criteriaPE
PROFILE 1007 (NCT00932893)IIICrizotinib vs Pem or Doc as second-lineALK(+) and 1 prior platinum-based chemoPFS
PROFILE 1014 (NCT01154140)IIICrizotinib + Pem + Cis/Carbo vs Pem + Cis/Carbo as first-lineALK(+) and chemotherapy-naivePFS
PROFILE 1005 (NCT00932451)IICrizotinib vs placebo as third-lineALK(+) and PD in arm B of study PROFILE 1007RR
PROFILE 1001 (NCT00965731)I/IICrizotinib + erlotinib vs erlotinib as second or third-lineAdenocarcinoma NSCLC and 1-2 prior chemoMTD
PROFILE 1001 (NCT01121575)ICrizotinib + PF0299804Acquired resistance to erlotinib or gefitinibMTD
Table 4 Ongoing phase II/III clinical trials involving targeted agents for patients with advanced or metastatic non-small cell lung cancer
Study designClinical trial IDPhaseStatusKey entry criteria
EGFR inhibition
Erlotinib vs docetaxelNCT00637910IIIRecruitingWT EGFR, prior platinum chemo, no prior taxanes
Erlotinib vs pazopanibNCT01027598IIActive, not recruiting1 prior chemo
Erlotinib + OSI-906NCT01221077IIRecruitingEGFR mutation (+), chemotherapy-naive
Erlotinib + ARQ197NCT01377376IIIRecruitingWT EGFR, prior platinum-based chemo
Erlotinib + ARQ197NCT01244191IIIRecruiting2 prior lines of chemo
Erlotinib + PC + BevNCT00976677IIActive, not recruitingNon-squamous, nonsmokers
Gefitinib (maintenance)NCT01404260IIIActive, not recruitingStable disease after chemo, EGFR unknown, never or light smokers
Gefitinib vs PemNCT00891579IIRecruitingWT EGFR, prior platinum-based chemo
AfatinibNCT00525148IIActive, not recruitingEGFR mutation (+)
AfatinibNCT00711594IIActive, not recruitingPrior platinum-based chemo, progressed after erlotinib or gefitinib
PF00299804NCT01000025IIIRecruiting1 prior chemo
PF00299804 vs erlotinibNCT01360554IIIRecruiting1 prior chemo
BRAF inhibition
AZD6244 + erlotinibNCT01229150IIRecruitingKRAS WT or KRAS mutant
DasatinibNCT01514864IIRecruitingTumors harboring DDR2 mutation or inactivating B-RAF mutation
AKT inhibition
MK-2206 + erlotinibNCT01294306IIRecruitingProgressed after initial response to erlotinib
MEK inhibition
GSK2118436NCT01336634IIRecruitingBRAF mutation (+)
HDAC inhibitor
Vorinostat + gefitinibNCT01027676II/IIIRecruitingprior platinum-based chemo
Vorinostat + bortezomibNCT00798720IICompleted recruiting2 prior chemo
Belinostat + Bev + PCNCT01090830IIRecruitingChemotherapy-naive
LBH589 + PemNCT00907179IIRecruiting1 prior chemo
KRAS mutations
AZD6244 + erlotinibNCT01229150IIRecruitingPrior platinum-based chemo
Erlotinib + ARQ197 vs single-agent chemoNCT01395758IIRecruitingKRAS mutation (+)
GSK1120212 vs docetaxelNCT01362296IIRecruitingKRAS mutation (+)