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. 2023 Jun 13;14:1137983. doi: 10.3389/fphar.2023.1137983

TABLE 1.

Summary of the study design, patient population and non-small cell lung cancer (NSCLC) drug used for each publication.

References (publication year) Clinical trial identifier Reporting country Study design Total number of cluster groups Total number of patients Age, median (range) Sex (M/F) Severity of Illness/NSCLC stage Co-morbidities Subgroups measured Drugs involved
Mizugaki et al. (2015) NCT01617928 Japan Open-label, Phase I Study 3 12 67 (44–73 years old) 10M 2F Stage IIIIB, Stage IV, Postoperative recurrence Smoker status Dose Carboplatin, Paclitaxel, Veliparib
Huang et al. (2020) NCT03201146 China Phase I Study 3 12 53.4 (42.2–63.4 years old) 7M
5F
Stage IVA,
Stage IVB
Smoker status Dose Apatinib, Carboplatin, Pemetrexed
Sebastian et al. (2019) N/A Germany & Switzerland Prospective, multicenter, open-label, uncontrolled phase I/IIa trial 4 46 64.7 (SD: 10.2) 29M
1 7F
Stage IIIB, Stage IV N/A Dose CV9201 (generated using proprietary RNActive® Technology)
Novello et al. (2014a) NCT01086254 Italy, France, Germany, Spain, United Kingdom Phase II, randomized, open-label, non-comparative study 2 119 58.7 (29–73 years old) 90M 29F Stage I,
Stage III,
Stage IV
Smoker status N/A Cisplatin, Iniparib, Gemcitabine
Cappuzzo et al. (2006) N/A Italy Phase II, randomized Study 2 117 72.5 (54–81 years old) 98M 19F Stage IIIB,
Stage IV
N/A Infusion Duration Chemotherapy, Gemcitabine
Srinivasa et al. (2020) N/A India Randomized prospective study 2 36 57 (45–65 years old) 33M 3F Stage IIIA, Stage IIIB N/A N/A Carboplatin, Cisplatin, Etoposide, Paclitaxel
Yoshioka et al. (2017) NCT01207011 Japan Randomized, open-label, phase III trial 2 197 20–75 years old 135M
62F
Stage IIIIB, Stage IV, Postoperative recurrence Smoker status N/A Amrubicin, Docetaxel
Johnson et al. (2013) NCT00257608 United States Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial 2 743 64 (23–88 years old) 389M, 354F Stage IIIB, Stage IV, Recurrent Smoker Status N/A Bevacizumab, Erlotinib
(Chemotherapy prior to trial)
EU Clinical Trials Register. (2011) MEK114653 (EU Clinicals Register) France, Greece, Hungary, Italy, Netherlands, South Korea, Spain, United States Phase II, Open-label, Multicenter, Randomized Study 2 134 (4 drop out) 61.2 (18–64 years old) 69M, 65F Stage IIIB, Stage IV N/A Crossover Phase Docetaxel, GSK1120212
Gridelli et al. (2001) N/A Italy Pilot Single-Stage Phase II Study 2 98 74 (70–82 years old) 83M,
15F
Stage IIIB, Stage IV N/A N/A Gemcitabine, Vinorelbine
Martoni et al. (1991) N/A Italy Phase I Trial 4 24 60 (36–68 years old) 24M,
0F
Stage IIIB,
Stage IV
N/A Dose,
LVEF values
Epirubicin
Sequist et al. (2013), Boehringer Ingelheim (2018a), Wu et al. (2018) NCT00949650 (LL3) Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, France, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, Malaysia, Peru, Philippines, Romania, Russia, South Korea, Taiwan, Thailand, Ukraine, United Kingdom, United States Global, randomized, open-label phase III study 2 345 60.3 (S.D. 10.1 years old) 121M, 224F Stage IIIB,
Stage IV
Smoker Status N/A Afatinib,
Cisplatin, Pemetrexed
Boehringer Ingelheim, (2018a) Boehringer Ingelheim. (2018b) NCT01121393 China, South Korea, Thailand Randomized, Open-label, Phase III Study 2 364 56.4 (SD: 10.9) 126M, 238F Stage IIIB,
Stage IV
Smoker Status N/A Afatinib (BIBW2992), Cisplatin, Gemcitabine
Boehringer Ingelheim (2020) NCT01466660 Australia, Canada, China, France, Germany, Hong Kong, Ireland, Norway, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom Randomised, Open-label Phase IIB Trial 2 319 62.4 (SD: 11.0) 122M, 197F Stage IIIB,
Stage IV
Smoker Status N/A Afatinib, Gefitinib
Hida et al. (2017) JapicCTI-132316 (Japan Pharmaceutical Information Centre) Japan Phase III, Open-label, Multicenter, Randomised Trial 2 207 60.2 (25–85 years old) 82M,
125F
Stage IIIIB, Stage IV, Postoperative recurrence Smoker Status N/A Alectinib, Crizotinib
Berghmans et al. (2013) NCT00622349 Belgium, France, Greece, Spain Phase III Trial 3 693 58 (28–84 years old) 523M,170F Stage IIB, Stage IIIA, Stage IIIB, Stage IV N/A N/A Cisplatin, Docetaxel, Gemcitabine, Ifosfamide
GlaxoSmithKline (2014) NCT01362296 France, Greece, Hungary, Italy, Netherlands, South Korea, Spain, United States Phase II, Open-label, Multicenter, Randomised Trial 2 134 61.2 (SD: 9.32) 69M,
65F
Stage IV Smoker Status N/A Docetaxel,
GSK1120212 (Trametinib)
Martoni et al. (1999) N/A Italy Pilot Study 2 212 61 (42–72 years old) 179M, 33F Stage IIIA, Stage IIIB, Stage IV, Recurrence N/A N/A Epirubicin, cisplatinum, vinorelbine
Reck et al. (2015) NCT00805194 Austria, Belarus, Belgium, Bulgaria, China, Croatia, Czech Republic, Denmark, France, Georgia, Germany, Greece, India, Israel, Italy, Lithuania, Poland, Portugal, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Switzerland, Ukraine, United Kingdom Randomized, Placebo-Controlled, Phase III trial 2 1314 59.8 955M,
359F
<Stage IIIB,
Stage IIIB,
Stage IV
Smoker Status N/A Docetaxel, Nintedanib
Saito et al. (2003) N/A Japan Parallel 2 25 61.8 (40–79 years old) 16M,
9F
Stage III,
Stage IV
N/A LVEF Carboplatin, Docetaxel,
Paclitaxel
Barlesi et al. (2018) NCT02395172 Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czech Republic, Denmark, Estonia, France, Hungary, Israel, Italy, Japan, Latvia, Mexico, Peru, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey, United Kingdom, and United States Open-label, multicentre, randomised Phase III trial 2 792 63.5 (57–69 years old) 542M
250F
Stage IIIB,
Stage IV,
Recurrent
NSCLC with disease progression after previous platinum doublet treatment>
Smoker Status N/A Avelumab, Docetaxel
Camidge et al. (2018) NCT02737501 Australia, Austria, Canada, Denmark, France, Germany, Hong Kong, Italy, South Korea, Luxembourg, Netherlands, Norway, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States Open-label, multicenter, randomized, international, Phase III trial 2 275 59 (27–89 years old) 125M
150F
Stage IIIB,
Stage IV
Smoker Status N/A Brigatinib, Crizotinib
Wachters et al. (2004) N/A Netherlands Randomised phase III trial 2 69 61 (43–76 years old) 49M
20F
Stage IIIA,
Stage IIIB
Stage IV
N/A LVEF Cisplatin, Epirubicin, Gemcitabine
Shaw et al. (2013) NCT00932893 Australia, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Netherlands, Poland, Russian Federation, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States Phase 3, Randomized, Open-label Study 2 347 50 (22–85 years old) 154M 193F Advanced Smoker Status N/A Crizotinib (PF-02341066), Docetaxel,
Pemetrexed
Solomon et al. (2014) NCT01154140 Australia, Austria, Belgium, Brazil, Canada, Chile, China, Finland, France, Germany, Hong Kong, India, Ireland, Italy, Japan, Luxembourg, Mexico, Netherlands, Norway, Peru, Portugal, Russian Federation, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, Ukraine, United Kingdom, United States Phase 3, Randomized, Open-label Study 2 343 53 (19–78 years old) 131M
212F
Advanced Smoker Status N/A Crizotinib, Carboplatin, Cisplatin, Pemetrexed
Bonomi et al. (2000) N/A United States A Phase III Study 3 574 61.8 365M
209F
Stage IIIB, Stage IV N/A Dose Cisplain,
Etoposide,
Paclitaxel
Zatloukal et al. (2004) N/A Czech Republic Prospective, randomized open, parallel group study 2 102 61.5 (42–75 years old) 69M
33F
Stage IIIA,
Stage IIIB
N/A N/A Cisplatin, Vinorelbine
Zarogoulidis et al. (2013) N/A Greece Four-arm Phase III Trial 4 229 62.5 187M
37F
Stage IIIB,
Stage IV
Smoker Status N/A Bevacizumab,
Carboplatin, Docetaxel, Erlotinib
Koch et al. (2011) NCT00300729 Sweden Double-blind, placebo-controlled multicentre Phase III Trial 2 316 65.5 (37–85 years old) 160M
156F
Stage IIIB,
Stage IV
Smoker Status N/A Celecoxib,
Chemotherapy (carboplatin/cisplatin/gemcitabine/vinorelbine)
Bi et al. (2019) NCT01503385 China A Phase II Randomized Clinical Trial 2 96 60 73M
23F
Stage IIIA,
Stage IIIB
Smoker Status N/A Celecoxib, Cisplatin,
Etoposide
Herbst et al. (2011) NCT00130728 12 countries including United States Double-blind, Placebo-Controlled, Randomised Phase 3 trial 2 636 64.9 341M
295F
N/A Smoker Status N/A Bevacizumab, Erlotinib
Kato et al. (2018); Seto et al. (2014) JapicCTI-111390 (Japan Pharmaceutical Information Centre) Japan Open-label, randomised, multicentre, Phase II Study 2 152 67 (59–73 years old) 56M
96F
Stage IIIB
Stage IV,
Postoperative recurrence
Smoker Status N/A Bevacizumab, Erlotinib
National Cancer Institute. (2019) NCT00126581 United States A Phase II Randomized, Open label Study 2 181 59 (32–81 years old) 74M
107F
Stage III,
Stage IV
Smoker Status N/A Carboplatin,
Erlotinib, Paclitaxel
Stathopoulos et al. (2004) N/A Greece Multicenter, randomized, phase III trial 2 360 65 (30–84 years old) 312M
48F
Stage IIIA,
Stage IIIB, Stage IV
N/A N/A Carboplatin, Paclitaxel, Vinorelbine
Valdivieso et al. (1984) N/A United States Prospective, randomised study 2 100 56.5 (33–78 years old) 79M
21F
N/A Biopsy Weekly VS. once every 3 weeks doxorubicin Cisplatin, Cyclo-phosphamide, Doxorubicin, Ftorafur
Baggstrom et al. (2017a) NCT00693992 United States Randomized, double-blind, placebo-controlled phase III trial 2 210 64.9 (25–89 years old) 117M
93F
Stage IIIB,
Stage IV
Smoker Status N/A Chemotherapy, Sunitinib
Paz-Ares et al. (2015) NCT00863746 Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Japan, South Korea, Netherlands, Pakistan, Peru, Phillippines, Poland, Russia, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States Phase III, randomized, double-blind, placebo-controlled trial 2 703 ≥18 years old 395M
308F
N/A Smoker Status N/A Best supportive care, Sorafenib
Novello et al. (2014b) NCT00460317 32 countries including Italy, Germany, Romania, Ukraine, United Kingdom, United States Phase 3, randomized, placebo-controlled, doubleblind study 2 360 60.8 (31–81 years old) 295M
65F
Stage IIIB,
Stage IV
Smoker Status N/A Carboplatin, Paclitaxel, Motesanib
Akamatsu et al. (2018) NCT02151981 Australia, Canada, China, France, Germany, Hong Kong, Hungary Italy, Japan, Mexico, Netherlands, Russia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States Randomized, open-label, phase III clinical trial 2 419 62.5 (20–90 years old) 150M
269F
N/A Smoker Status N/A Carboplatin, Cisplatin, Pemetrexed, Osimertinib
Kosmidis et al. (2008) N/A Greece Phase III Study 2 452 63 (36–83 years old) 378M
74F
Stage IIIB,
Stage IV
N/A N/A Carboplatin, Paclitaxel,
Gemcitabine
Reinmuth et al. (2019) NCT02364999 Australia, Brazil, Bulgaria, Chile, Croatia, Czech Republic, France, Germany, Greece, Hungary, India, Italy, Japan, South Korea, Malaysia, Netherlands, Philippines, Poland, Romania, Russia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United States Multinational, double-blind, randomized, parallel-group study 2 719 61.5 (25–87 years old) 467M
252F
Stage IIIB, Stage IV, Recurrent Smoker Status N/A Bevacizumab, Carboplatin, Paclitaxel,
PF-06439535
Blumenschein et al. (2010) NCT00094835 United States Multicenter, Open-label, Dose-finding, Phase IB study of motesanib 3 45 61.3 (32–79 years old) 29M
16F
Stage IIIB,
Stage IV
Smoker Status N/A Carboplatin, Paclitaxel,
Panitumumab, Motesanib
Choy et al. (2013) NCT00482014 India, United States Open-label, Randomised Trial 2 98 63.6 (43.7–85.2 years old) 61M
37F
Stage IIIA,
Stage IIIB
N/A N/A Carboplatin,
Cisplatin
Pemetrexed
William et al. (2007) N/A United States Open-label, Phase I, Dose-escalationStudy 4 21 52 (38–71 years old) 13M
8F
Stage IV N/A Dose Cisplatin, Docetaxel, Motexafin gadolinium
Chang et al. (1993) N/A United States Phase II Study 3 103 61.3 (31–85 years old) 70M
33F
Stage IV N/A N/A Merbarone, Piroxantrone, Taxol
Kubota et al. (2017) JapicCTI-121887 (Japan Primary Registries Network) Japan, South Korea, Hong Kong, Taiwan Phase III, Randomized, Placebo-Controlled, Double-blind Study 2 401 65 (Upper Quartile: 58; Lower Quartile: 70) 288M
113F
Stage IV, Recurrent Smoker Status N/A Carboplatin, Motesanib, Paclitaxel
Zinner et al. (2015) NCT00948675 United States Multicenter, Randomized, Open-label, US-only Phase III Trial 2 361 65.6 (38.4–86.2 years old) 209M
152F
Stage IV Smoker Status N/A Bevacizumab, Carboplatin, Paclitaxel Pemetrexed
Heigener et al. (2013) NCT00160069 Germany Prospective, Multicenter, Phase II study 3 128 63 83M
45F
Stage IIIB, Stage IV N/A Dose, Duration of Infusion Sagopilone
Jie Wang et al. (2018) N/A China Randomised Controlled Trial 2 128 No mean/median (36–76 years old) 96M
32F
N/A N/A N/A Cisplatin, Endostar, Pemetrexed
Eli Lilly and Company (2019a) NCT01469000 China, Japan, South Korea, Taiwan Multicenter, Randomized, open-label, parallel-arm, phase II study 2 191 61.71 (S.D.: 9.38) 68M
123F
Stage IV N/A N/A Gefitinib, Pemetrexed
Douillard (2004) N/A Belgium, Canada, France, Germany, Italy, Spain, United States Randomized, Double-blind, Placebo-controlled, Phase II Feasibility Study 2 75 61.4 56M
19F
Stage IIIB, Stage IV N/A N/A BMS-275291, Carboplatin, Paclitaxel
Butts et al. (2007) N/A Canada, United States Multicenter, Open-label, Randomized Phase II study 2 131 66 (35–84 years old) 58M
73F
Stage IIIB
Stage IV, Recurrent
N/A N/A Carboplatin, Cisplatin, Cetuximab, Gemcitabine
Fukuda et al. (2019) UMIN000008771 (University Hospital Medical Information Network) Japan Randomised Phase II Study 2 40 78 (75–83 years old) 23M
17F
Stage IIIB,
Stage IV,
Postoperative recurrence
Smoker Status N/A Bevacizumab,
Pemetrexed
Passardi et al. (2008) N/A Italy Randomized Phase II Trial 2 81 63 (35–77 years old) 65M
16F
Stage IV N/A N/A Docetaxel,
Gemcitabine
Gatzemeier et al. (2004) N/A Canada, Italy, Germany, Netherlands, United Kingdom Randomized, Open-label, Phase II study 2 101 58.5 (35–76 years old) 63M
38F
Stage IB,
Stage IIIB, Stage IV
N/A N/A Cisplatin, Gemcitabine, Trastuzumab
Park et al. (2017) NCT01282151 South Korea Open-label, Multicenter Prospective Phase III Study 2 148 63.3 103M
45F
Stage IIIB, Stage IV Smoker Status N/A Cisplatin, Docetaxel, Pemetrexed
Movsas et al. (2005) N/A Canada, United States Randomised Trial 2 242 ≥18 years old 150M
92F
Stage IIA, Stage IIB, Stage IIIA, Stage IIIB N/A N/A Amifostine, Carboplatin, Paclitaxel
Jänne et al. (2014) N/A Canada, Germany, Spain, United States Randomized, Double-Blind, Phase II Trial 3 200 61.4 (27.8–87.8 years old) 127M
68F
Stage IIIB, Stage IV Smoker Status Dose Cisplatin, Gemcitabine, LY293111
Groen et al. (2011) N/A Netherlands Randomized, Placebo-Controlled Phase III Study 2 561 61 (33–84 years old) 355M
206F
Stage IIIB, Stage IV N/A N/A Carboplatin, Celecoxib, Docetaxel
Currow et al. (2017) NCT01395914 Australia, Belarus, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Poland, Russia, Serbia, Slovenia, Spain, Ukraine Double-blind, safety extension Phase III Study 2 513 62.0 387M
126F
Stage IIIA,
Stage IIIB, Stage IV
N/A N/A Anamorelin, Placebo
Langer et al. (2017) NCT00789373 Australia, Belgium, Canada, Finland, France, Germany, Greece, India, Italy, Netherlands, Poland, Portugal, Romania, Spain, Turkey, United Kingdom Phase 3, Double-Blind, Placebo-Controlled Study 2 939 61.3 (24.4–83.0 years old) 577M
362F
Stage IIIB, Stage IV Smoker Status N/A Cisplatin, Pemetrexed, Placebo
Kotsakis et al. (2015) NCT00620971 Greece A Multicenter, Randomized, Phase II study 2 77 59 (36–77 years old) 57M
20F
Stage IIIB, Stage IV Smoker Status N/A Bevacizumab, Cisplatin, Docetaxel, Gemcitabine, Vinorelbine
Eli Lilly and Company (2015) NCT00112294 United States A Phase III, Randomised, Open Label Study 2 676 64 (S.D.: 10.2) 396M
280F
N/A N/A N/A Carboplatin, Cetuximab, Taxane (Paclitaxel/Docetaxel)
GlaxoSmithKline (2019) NCT01868022 Belgium, Denmark, Netherlands, Russia, Spain, United Kingdom, United States Multi-arm, Non-randomized, Open-Label Phase IB Study 9 65 66.52 (S.D.: 3.08) 52M
13F
Stage IIIB, Stage IV N/A Dose Carboplatin, Cisplatin,
Docetaxel, GSK3052230, Paclitaxel, Pemetrexed
Lara et al. (2016) N/A United States Randomised, Phase II Selection Design Trial 2 59 73.1 (40.9–85.9 years old) 24M
35F
Stage IIIB, Stage IV Smoker Status N/A Carboplatin, Erlotinib, Paclitaxel
Wu et al. (2020) NCT01982955 China, Italy, Malaysia, Singapore, South Korea Spain, Taiwan Open-label, randomized, Phase 1b/2 study 5 88 N/A 36M
52F
Advanced N/A N/A Carboplatin, Cisplatin, Gefitinib, Pemetrexed,
Tepotinib,
Umsawasdi et al. (1989) N/A N/A Randomised Study 2 102 56.5 (33–78 years old) 71M
31F
Stage III N/A N/A Cisplatin, Cyclophosphamide, Doxorubicin
Cortot et al. (2020) NCT01763671 France Double-arm, Randomised, Open-label, Multicentre, Phase III Clinical Trial 2 166 59.7 (18.6–81.8 years old) 120M
46F
Stage III, Stage IV Smoker Status N/A Bevacizumab, Docetaxel, Paclitaxel
AstraZeneca (2021) NCT01933932 Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States A Phase III, Double-Blind, Randomised, Placebo-Controlled Study 2 510 61.4 (S.D.: 8.3) 303M
207F
Stage IIIB, Stage IV N/A N/A Docetaxel, Selumetinib
Johnson et al. (2004) N/A United States Randomized Phase II Study 3 99 ≥18 years old 60M
39F
Stage IIIB, Stage IV N/A Dose Bevacizumab, Carboplatin, Paclitaxel
Eli Lilly and Company (2022) NCT00981058 Australia, Austria, Belgium, Brazil, Canada, Croatia, France, Germany, Greece, Hungary, Italy, South Korea, Philippines, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, Spain, Taiwan, Thailand, United Kingdom, United States Multinational, Randomized, Multicenter, Open-label, Phase III Study 2 1093 62 (32–86 years old) 908M
185F
Stage IIIB, Stage IV Smoker Status N/A Cisplatin, Gemcitabine, Necitumumab
Eli Lilly and Company (2021) NCT00982111 Australia, Austria, Belgium, Brazil, Canada, Croatia, France, Germany, Greece, Hungary, Italy, Poland, Portugal, Romania, Russia, Slovakia, South Africa, Spain, United Kingdom, United States Multinational, Randomized, Multicenter, Open-label Phase III Study 2 633 61 (26–88 years old) 424M
209F
Stage IIIB, Stage IV Smoker Status N/A Cisplatin, Pemetrexed, Necitumumab
Eli Lilly and Company (2019b) NCT01769391 Germany, South Korea, Mexico, Poland, Russia, United States Randomized, Multicenter, Open-Label, Phase II Study 2 167 65.3 131M
36F
Stage IV N/A N/A Carboplatin, Paclitaxel, Necitumumab