1. bookVolume 51 (2017): Issue 3 (September 2017)
Journal Details
License
Format
Journal
eISSN
1581-3207
First Published
30 Apr 2007
Publication timeframe
4 times per year
Languages
English
access type Requires Authentication

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors

Published Online: 18 Jul 2017
Volume & Issue: Volume 51 (2017) - Issue 3 (September 2017)
Page range: 241 - 251
Received: 03 May 2017
Accepted: 09 Jun 2017
Journal Details
License
Format
Journal
eISSN
1581-3207
First Published
30 Apr 2007
Publication timeframe
4 times per year
Languages
English
AbstractBackground

When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.

Methods

Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson’s correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.

Results

The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with non-squamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.

Conclusions

Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.

Key words

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129-39. 10.1056/NEJMoa040938LynchTJBellDWSordellaRGurubhagavatulaSOkimotoRABranniganBWActivating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinibN Engl J Med200435021293910.1056/NEJMoa040938Open DOISearch in Google Scholar

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-57. 10.1056/NEJMoa0810699MokTSWuYLThongprasertSYangCHChuDTSaijoNGefitinib or carboplatin-paclitaxel in pulmonary adenocarcinomaN Engl J Med20093619475710.1056/NEJMoa0810699Open DOISearch in Google Scholar

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 2015; 26: 1877-83. 10.1093/annonc/mdv276ZhouCWuYLChenGFengJLiuXQWangCFinal overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)Ann Oncol20152618778310.1093/annonc/mdv276Open DOISearch in Google Scholar

Sequist LV, Yang JC, Yamamoto N, O’Byrne K, Hirsh V, Mok T, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013; 31: 3327-34. 10.1200/JCO.2012.44.2806SequistLVYangJCYamamotoNO’ByrneKHirshVMokTPhase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutationsJ Clin Oncol20133133273410.1200/JCO.2012.44.2806Open DOISearch in Google Scholar

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13: 239-46. 10.1016/S1470-2045(11)70393-XRosellRCarcerenyEGervaisRVergnenegreAMassutiBFelipEErlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trialLancet Oncol2012132394610.1016/S1470-2045(11)70393-XOpen DOISearch in Google Scholar

Inoue A, Yoshida K, Morita S, Imamura F, Seto T, Okamoto I, et al. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 2016; 46: 462-7. doi.org/10.1093/jjco/hyw014InoueAYoshidaKMoritaSImamuraFSetoTOkamotoICharacteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patientsJpn J Clin Oncol2016464627doi.org/10.1093/jjco/hyw014Open DOISearch in Google Scholar

Zhou C, Yao LD. Strategies to improve outcomes of patients with EGRF-mutant non-small cell lung cancer: Review of the literature. J Thorac Oncol 2016; 11: 174-86. 10.1016/j.jtho.2015.10.002ZhouCYaoLDStrategies to improve outcomes of patients with EGRF-mutant non-small cell lung cancer: Review of the literatureJ Thorac Oncol2016111748610.1016/j.jtho.2015.10.00226845114Open DOISearch in Google Scholar

Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 1. J Clin Oncol 2004; 22: 777-84. 10.1200/JCO.2004.08.001GiacconeGHerbstRSManegoldCScagliottiGRosellRMillerVGefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 1J Clin Oncol2004227778410.1200/JCO.2004.08.00114990632Open DOISearch in Google Scholar

Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 2. J Clin Oncol 2004; 22: 785-94. 10.1200/JCO.2004.07.215HerbstRSGiacconeGSchillerJHNataleRBMillerVManegoldCGefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial - INTACT 2J Clin Oncol2004227859410.1200/JCO.2004.07.21514990633Open DOISearch in Google Scholar

Herbst RS, Prager D, Herman R, Fehrenbacher L, Johnson BE, Sandler A, et al. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005; 23: 5892-9. 10.1200/JCO.2005.02.840HerbstRSPragerDHermanRFehrenbacherLJohnsonBESandlerATRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancerJ Clin Oncol2005235892910.1200/JCO.2005.02.84016043829Open DOISearch in Google Scholar

Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, et al. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: The Tarceva Lung Cancer Investigation Trial. J Clin Oncol 2007; 25: 1545-52. 10.1200/JCO.2005.05.1474GatzemeierUPluzanskaASzczesnaAKaukelERoubecJDe RosaFPhase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: The Tarceva Lung Cancer Investigation TrialJ Clin Oncol20072515455210.1200/JCO.2005.05.147417442998Open DOISearch in Google Scholar

Ratti M, Tomasello G. Emerging combination therapies to overcome resistance in EGFR-driven tumors. Anticancer Drugs 2014; 25: 127-39. 10.1097/CAD.0000000000000035RattiMTomaselloGEmerging combination therapies to overcome resistance in EGFR-driven tumorsAnticancer Drugs2014251273910.1097/CAD.000000000000003524113593Open DOISearch in Google Scholar

Steuer CE, Khuri FR, Ramalingam SS. The next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancer. Cancer 2015; 121: E1-E6. 10.1002/cncr.29139SteuerCEKhuriFRRamalingamSSThe next generation of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of lung cancerCancer2015121E1E610.1002/cncr.2913925521095Open DOISearch in Google Scholar

Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med 2015; 372: 1689-99. 10.1056/NEJMoa1411817JännePAYangJCKimDWPlanchardDOheYRamalingamSSAZD9291 in EGFR inhibitor-resistant non-small-cell lung cancerN Engl J Med201537216899910.1056/NEJMoa141181725923549Open DOISearch in Google Scholar

Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005; 23: 5900-909. 10.1200/JCO.2005.02.857EberhardDAJohnsonBEAmlerLCGoddardADHeldensSLHerbstRSMutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinibJ Clin Oncol200523590090910.1200/JCO.2005.02.85716043828Open DOISearch in Google Scholar

Reck M. Beyond the TRIBUTE trial: integrating HER1/EGFR tyrosine kinase inhibitors with chemotherapy in advanced NSCLC. Future Oncol 2006; 2: 47-51. 10.2217/14796694.2.1.47ReckMBeyond the TRIBUTE trial: integrating HER1/EGFR tyrosine kinase inhibitors with chemotherapy in advanced NSCLCFuture Oncol20062475110.2217/14796694.2.1.4716556072Open DOISearch in Google Scholar

Tsai CM, Chen JT, Chiu CH, Lai CL, Hsiao SY, Chang KT. Combined epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor and chemotherapy in non-small-cell lung cancer: chemo-refractoriness of cells harboring sensitizing-EGFR mutations in the presence of gefitinib. Lung Cancer 2013; 82: 305-12. 10.1016/j.lungcan.2013.08.028TsaiCMChenJTChiuCHLaiCLHsiaoSYChangKTCombined epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor and chemotherapy in non-small-cell lung cancer: chemo-refractoriness of cells harboring sensitizing-EGFR mutations in the presence of gefitinibLung Cancer2013823051210.1016/j.lungcan.2013.08.02824055492Open DOISearch in Google Scholar

Davies AM, Ho C, Lara PN Jr, Mack P, Gumerlock PH, Gandara DR. Pharmacodynamic separation of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy in non-small-cell lung cancer. Clin Lung Cancer 2006; 7: 385-8. 10.3816/CLC.2006.n.021DaviesAMHoCLaraPNJrMackPGumerlockPHGandaraDRPharmacodynamic separation of epidermal growth factor receptor tyrosine kinase inhibitors and chemotherapy in non-small-cell lung cancerClin Lung Cancer20067385810.3816/CLC.2006.n.02116800963Open DOISearch in Google Scholar

Mahaffey CM, Davies AM, Lara PN Jr, Pryde B, Holland W, Mack PC, et al. Schedule-dependent apoptosis in K-ras mutant non-small-cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separation. Clin Lung Cancer 2007; 8: 548-53. 10.3816/clc.2007.n.041MahaffeyCMDaviesAMLaraPNJrPrydeBHollandWMackPCSchedule-dependent apoptosis in K-ras mutant non-small-cell lung cancer cell lines treated with docetaxel and erlotinib: rationale for pharmacodynamic separationClin Lung Cancer200785485310.3816/clc.2007.n.04118186959Open DOISearch in Google Scholar

Piperdi B, Ling Y-H, Kroog G, Perez-Soler R. Schedule-dependent interaction between epidermal growth factor inhibitors (EGFRI) and G2/M blocking chemotherapeutic agents (G2/MB) on human NSCLC cell lines in vitro. J Clin Oncol 2004; 22(14S): 7028. PMID: 28016090PiperdiBLingY-HKroogGPerez-SolerRSchedule-dependent interaction between epidermal growth factor inhibitors (EGFRI) and G2/M blocking chemotherapeutic agents (G2/MB) on human NSCLC cell lines in vitroJ Clin Oncol20042214S7028PMID: 2801609010.1200/jco.2004.22.90140.7028Search in Google Scholar

Solit DB, She Y, Lobo J, Kris MC, Scher HI, Rosen N, et al. Pulsatile administration of epidermal growth factor receptor inhibitor gefitinib is significantly more effective than continuous dosing for sensitizing tumors to paclitaxel. Clin Cancer Res 2005; 11: 1983-9. 10.1158/1078-0432.CCR-04-1347SolitDBSheYLoboJKrisMCScherHIRosenNPulsatile administration of epidermal growth factor receptor inhibitor gefitinib is significantly more effective than continuous dosing for sensitizing tumors to paclitaxelClin Cancer Res2005111983910.1158/1078-0432.CCR-04-1347Open DOISearch in Google Scholar

Bartholomeusz C, Yamasaki F, Saso H, Kurisu K, Hortobagyi GN, Ueno NT. Gemcitabine overcomes erlotinib resistance in EGFR-overexpressing cancer cells through downregulation of Akt. J Cancer 2011; 2: 435-42. 10.7150/jca.2.435BartholomeuszCYamasakiFSasoHKurisuKHortobagyiGNUenoNTGemcitabine overcomes erlotinib resistance in EGFR-overexpressing cancer cells through downregulation of AktJ Cancer201124354210.7150/jca.2.435Open DOISearch in Google Scholar

Kanda S, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Sekine I, et al. Cytotoxic chemotherapy may overcome the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy. Lung Cancer 2015; 89: 287-93. 10.1016/j.lungcan.2015.06.016KandaSHorinouchiHFujiwaraYNokiharaHYamamotoNSekineICytotoxic chemotherapy may overcome the development of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapyLung Cancer2015892879310.1016/j.lungcan.2015.06.016Open DOISearch in Google Scholar

La Salvia A, Rossi A, Galetta D, Gobbini E, De Luca E, Novello S, et al. Intercalated chemotherapy and epidermal growth factor receptor inhibitors for patients with advanced non-small-cell lung cancer: A systematic review and meta-analysis. Clin Lung Cancer 2017; 18: 23-33. 10.1016/j.cllc.2016.08.006La SalviaARossiAGalettaDGobbiniEDe LucaENovelloSIntercalated chemotherapy and epidermal growth factor receptor inhibitors for patients with advanced non-small-cell lung cancer: A systematic review and meta-analysisClin Lung Cancer201718233310.1016/j.cllc.2016.08.006Open DOISearch in Google Scholar

Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small cell lung cancer with adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 2015; 5: 2892-11. PMID: 26609494MidhaADeardenSMcCormackREGFR mutation incidence in non-small cell lung cancer with adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII)Am J Cancer Res20155289211PMID: 26609494Search in Google Scholar

Mok TS, Wu YL, Yu CJ, Zhou C, Chen YM, Zhang L, et al. Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 2009; 27: 5080-7. 10.1200/JCO.2008.21.5541MokTSWuYLYuCJZhouCChenYMZhangLRandomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small-cell lung cancerJ Clin Oncol2009275080710.1200/JCO.2008.21.5541Open DOISearch in Google Scholar

Hirsch FR, Kabbinavar F, Eisen T, Martins R, Schnell FM, Dziadziuszko R, et al. A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer. J Clin Oncol 2011; 29: 3567-73. 10.1200/JCO.2010.34.4929HirschFRKabbinavarFEisenTMartinsRSchnellFMDziadziuszkoRA randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancerJ Clin Oncol20112935677310.1200/JCO.2010.34.4929Open DOISearch in Google Scholar

Aerts JG, Codrington H, Lankheet NAG, Burgers S, Biesma B, Dingemans AM, et al. A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: The NVALT-10 study. Ann Oncol 2013; 24: 2860-5. 10.1093/annonc/mdt341AertsJGCodringtonHLankheetNAGBurgersSBiesmaBDingemansAMA randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: The NVALT-10 studyAnn Oncol2013242860510.1093/annonc/mdt341Open DOISearch in Google Scholar

Lee DH, Lee JS, Kim SW, Rodrigues-Pereira J, Han B, Song XQ, et al. Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer. Eur J Cancer 2013; 49: 3111-21. 10.1016/j.ejca.2013.06.035LeeDHLeeJSKimSWRodrigues-PereiraJHanBSongXQThree-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancerEur J Cancer20134931112110.1016/j.ejca.2013.06.035Open DOISearch in Google Scholar

Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT 2): a randomised, double blind trial. Lancet Oncol 2013; 14: 777-86. 10.1016/S1470-2045(13)70254-7WuYLLeeJSThongprasertSYuCJZhangLLadreraGIntercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT 2): a randomised, double blind trialLancet Oncol2013147778610.1016/S1470-2045(13)70254-7Open DOISearch in Google Scholar

Auliac JB, Chouaid C, Greillier L, Monnet I, Le Caer H, Falchero L, et al. Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study. Lung Cancer 2014; 85: 415-9. 10.1016/j.lungcan.2014.07.006AuliacJBChouaidCGreillierLMonnetILe CaerHFalcheroLRandomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 studyLung Cancer201485415910.1016/j.lungcan.2014.07.00625082565Open DOISearch in Google Scholar

Karavasilis V, Kosmidis P, Syrigos KN, Mavropoulou P, Dimopoulos MA, Kotoula V, et al. Docetaxel and intermittent erlotinib in patients with metastatic Non-Small Cell Lung Cancer; a phase II study from the Hellenic Cooperative Oncology Group. Anticancer Res 2014; 34: 5649-55. PMID: 25275069KaravasilisVKosmidisPSyrigosKNMavropoulouPDimopoulosMAKotoulaVDocetaxel and intermittent erlotinib in patients with metastatic Non-Small Cell Lung Cancer; a phase II study from the Hellenic Cooperative Oncology GroupAnticancer Res201434564955PMID: 25275069Search in Google Scholar

Mok TS, Gaeter SL, Iannotti N, Thongprasert S, Spira A, Smith D, et al. Randomized phase II study of two intercalated combinations of eribulin mesylate and erlotinib in patients with previously treated advanced non-small-cell lung cancer. Ann Oncol 2014; 25: 1578-84. 10.1093/annonc/mdu174MokTSGaeterSLIannottiNThongprasertSSpiraASmithDRandomized phase II study of two intercalated combinations of eribulin mesylate and erlotinib in patients with previously treated advanced non-small-cell lung cancerAnn Oncol20142515788410.1093/annonc/mdu174Open DOISearch in Google Scholar

Yu H, Zhang J, Wu X, Luo Z, Wang H, Sun S, et al. A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancer. Cancer Biol Ther 2014; 15: 832-9. 10.4161/cbt.28874YuHZhangJWuXLuoZWangHSunSA phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non-squamous non-small cell lung cancerCancer Biol Ther201415832910.4161/cbt.28874Open DOISearch in Google Scholar

Choi YJ, Lee DH, Choi CM, Lee JS, Lee SJ, Ahn JH, et al. Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naive non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFR. BMC Cancer 2015; 15: 763. 10.1186/s12885-015-1714yChoiYJLeeDHChoiCMLeeJSLeeSJAhnJHRandomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naive non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcinoma or mutated EGFRBMC Cancer20151576310.1186/s12885-015-1714yOpen DOISearch in Google Scholar

Juan Ó, Aparisi F, Sánchez-Hernandez A, Muñoz-Langa J, Esquerdo G, García-Sanchez J, et al. Intercalated dosing schedule of erlotinib and docetaxel as a therapeutic strategy to avoid antagonism and optimize its benefits in advanced non-small-cell lung cancer. A randomized phase II clinical trial. Clin Lung Cancer 2015; 16: 193-9. 10.1016/j.cllc.2014.11.006JuanÓAparisiFSánchez-HernandezAMuñoz-LangaJEsquerdoGGarcía-SanchezJIntercalated dosing schedule of erlotinib and docetaxel as a therapeutic strategy to avoid antagonism and optimize its benefits in advanced non-small-cell lung cancer. A randomized phase II clinical trialClin Lung Cancer201516193910.1016/j.cllc.2014.11.006Open DOISearch in Google Scholar

Lu S, Jian H, Li W, Yong MZ, Huang JJ, Feng J, et al. Intercalating and maintenance use of gefitinib plus chemotherapy versus chemotherapy alone in selected advanced NSCLC (ISCAN,CTONG-1102): a multicentre, open-label, randomised, phase 3 study. [abstract]. J Clin Oncol 2015; 33(Suppl): abstr 8042. ClinicalTrials.gov Identifier: NCT01404260LuSJianHLiWYongMZHuangJJFengJIntercalating and maintenance use of gefitinib plus chemotherapy versus chemotherapy alone in selected advanced NSCLC (ISCAN,CTONG-1102): a multicentre, open-label, randomised, phase 3 study. [abstract]J Clin Oncol201533(Suppl): abstr8042ClinicalTrials.gov Identifier: NCT0140426010.1200/jco.2015.33.15_suppl.8042Search in Google Scholar

Michael M, White SC, Abdi E, Nott L, Clingan P, Zimet A, et al. Multicenter randomized, open-label phase II trial of sequential erlotinib and gemcitabine compared with gemcitabine monotherapy as first-line therapy in elderly or ECOG PS two patients with advanced NSCLC. Asia Pac J Clin Oncol 2015; 11: 4-14. 10.1111/ajco.12178MichaelMWhiteSCAbdiENottLClinganPZimetAMulticenter randomized, open-label phase II trial of sequential erlotinib and gemcitabine compared with gemcitabine monotherapy as first-line therapy in elderly or ECOG PS two patients with advanced NSCLCAsia Pac J Clin Oncol20151141410.1111/ajco.12178Open DOISearch in Google Scholar

Han B, Zhang Y, Jin B, Chu T, Gu A, Xu J. Combination of chemotherapy and gefitinib as first-line treatment of patients with advanced lung adenocarcinoma and sensitive EGFR mutations: a randomized controlled trial. J Thorac Oncol 2016; 11(Suppl 4): S113-4. 10.1016/S1556-0864(16)30244-1HanBZhangYJinBChuTGuAXuJCombination of chemotherapy and gefitinib as first-line treatment of patients with advanced lung adenocarcinoma and sensitive EGFR mutations: a randomized controlled trialJ Thorac Oncol201611(Suppl 4)S113410.1016/S1556-0864(16)30244-1Open DOISearch in Google Scholar

Lara PN Jr, Moon J, Hesketh PJ, Redman MW, Williamson SK, Akerley WL 3rd, et al. SWOG S0709: Randomized Phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assay. J Thorac Oncol 2016; 11: 420-5. 10.1016/j.jtho.2015.11.003LaraPNJrMoonJHeskethPJRedmanMWWilliamsonSKAkerleyWL 3rdSWOG S0709: Randomized Phase II trial of erlotinib versus erlotinib plus carboplatin/paclitaxel in patients with advanced non-small cell lung cancer and impaired performance status as selected by a serum proteomics assayJ Thorac Oncol201611420510.1016/j.jtho.2015.11.003477536626725184Open DOISearch in Google Scholar

Li T, Piperdi B, Walsh WV, Kim M, Beckett A, Gucalp R, et al. Randomized phase II study of pharmacodynamic separation of pemetrexed and intercalated erlotinib versus pemetrexed alone for advanced non-small cell lung cancer. Clin Lung Cancer 2017; 18: 60-7. 10.1016/j.cllc.2016.10.003LiTPiperdiBWalshWVKimMBeckettAGucalpRRandomized phase II study of pharmacodynamic separation of pemetrexed and intercalated erlotinib versus pemetrexed alone for advanced non-small cell lung cancerClin Lung Cancer20171860710.1016/j.cllc.2016.10.003549770227919627Open DOISearch in Google Scholar

Lee JS, Lee YJ, Kim HY, Nam B-H, Lee GK, Kim HT, et al. Randomized phase II trial of intercalated gefitinib (G) and pemetrexed/cisplatin (Pem/Cis) for never-smokers with chemo-naïve stage IIIB/IV lung adenocarcinoma (LADC). [abstract]. J Clin Oncol 2016; 34: e20505. ClinicalTrials.gov Identifier: NCT01502202LeeJSLeeYJKimHYNamB-HLeeGKKimHTRandomized phase II trial of intercalated gefitinib (G) and pemetrexed/cisplatin (Pem/Cis) for never-smokers with chemo-naïve stage IIIB/IV lung adenocarcinoma (LADC). [abstract]J Clin Oncol201634e20505ClinicalTrials.gov Identifier: NCT0150220210.1200/JCO.2016.34.15_suppl.e20505Search in Google Scholar

Yoon S, Lee D-H, Kim D, Choi C-M, Kim S-W. Randomized Phase II trial comparing intercalation of afatinib to pemetrexed with pemetrexed alone after failure of platinum doublet therapy. [abstract] J Thorac Oncol 2017; 12(Suppl 1): S926. abstr P2.03A-061YoonSLeeD-HKimDChoi C-MKimS-WRandomized Phase II trial comparing intercalation of afatinib to pemetrexed with pemetrexed alone after failure of platinum doublet therapy. [abstract]J Thorac Oncol201712(Suppl 1)S926abstr P2.03A-06110.1016/j.jtho.2016.11.1271Search in Google Scholar

Oshita F, Saito H, Murakami S, Kondo T, Yamada K. Phase II study of paclitaxel and irinotecan with intercalated gefitinib in patients with advanced non-small-cell lung cancer. Am J Clin Oncol 2010; 33: 66-9. 10.1097/COC.0b013e31819ccc6dOshitaFSaitoHMurakamiSKondoTYamadaKPhase II study of paclitaxel and irinotecan with intercalated gefitinib in patients with advanced non-small-cell lung cancerAm J Clin Oncol20103366910.1097/COC.0b013e31819ccc6d19786849Open DOISearch in Google Scholar

Sangha R, Davies AM, Lara PN Jr, Mack PC, Beckett LA, Hesketh PJ, et al. Intercalated erlotinib-docetaxel dosing schedules designed to achieve pharmacodynamic separation: results of a phase I/II trial. J Thorac Oncol 2011; 6: 2112-9. 10.1097/JTO.0b013e31822ae061SanghaRDaviesAMLaraPNJrMackPCBeckettLAHeskethPJIntercalated erlotinib-docetaxel dosing schedules designed to achieve pharmacodynamic separation: results of a phase I/II trialJ Thorac Oncol201162112910.1097/JTO.0b013e31822ae061321983421892109Open DOISearch in Google Scholar

Minami S, Kijima T, Hamaguchi M, Nakatani T, Koba T, Takahashi R, et al. Phase II study of pemetrexed plus intermittent erlotinib combination therapy for pretreated advanced non-squamous non-small cell lung cancer with documentation of epidermal growth factor receptor mutation status. Lung Cancer 2013; 82: 271-5. 10.1016/j.lungcan.2013.07.022MinamiSKijimaTHamaguchiMNakataniTKobaTTakahashiRPhase II study of pemetrexed plus intermittent erlotinib combination therapy for pretreated advanced non-squamous non-small cell lung cancer with documentation of epidermal growth factor receptor mutation statusLung Cancer201382271510.1016/j.lungcan.2013.07.02223993733Open DOISearch in Google Scholar

Yoshimura N, Okishio K, Mitsuoka S, Kimura T, Kawaguchi T, Kobayashi M, et al. Prospective assessment of continuation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of pemetrexed. J Thorac Oncol 2013; 8: 96-101. 10.1097/JTO.0b013e3182762bfbYoshimuraNOkishioKMitsuokaSKimuraTKawaguchiTKobayashiMProspective assessment of continuation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of pemetrexedJ Thorac Oncol201389610110.1097/JTO.0b013e3182762bfb23207920Open DOISearch in Google Scholar

Kim YH, Nishimura T, Ozasa H, Nagai H, Sakamori Y, Iwata T, et al. Phase II study of pemetrexed and erlotinib in pretreated nonsquamous non-small-cell lung cancer patients without an EGFR mutation. Chemotherapy 2013; 59: 414-9. 10.1159/000363731KimYHNishimuraTOzasaHNagaiHSakamoriYIwataTPhase II study of pemetrexed and erlotinib in pretreated nonsquamous non-small-cell lung cancer patients without an EGFR mutationChemotherapy201359414910.1159/00036373125034625Open DOISearch in Google Scholar

Fang H, Lin RY, Sun MX, Wang Q, Zhao YL, Yu JL, et al. Efficacy and survival-associated factors with gefitinib combined with cisplatin and gemcitabine for advanced non- small cell lung cancer. Asian Pac J Cancer Prev 2014; 15: 10967-70. 10.7314/APJCP.2014.15.24.10967FangHLinRYSunMXWangQZhaoYLYuJLEfficacy and survival-associated factors with gefitinib combined with cisplatin and gemcitabine for advanced non- small cell lung cancerAsian Pac J Cancer Prev201415109677010.7314/APJCP.2014.15.24.1096725605210Open DOISearch in Google Scholar

Yang J, Shi Y, Zhang X, Xu J, Wang B, Hao X et al. Phase II trial of paclitaxel-carboplatin with intercalated gefitinib for untreated, epidermal growth factor receptor gene mutation status unknown non-small cell lung cancer. Thorac Cancer 2014; 5: 149-54. 10.1111/1759-7714.12074YangJShiYZhangXXuJWangBHaoXPhase II trial of paclitaxel-carboplatin with intercalated gefitinib fountreated epidermal growth factor receptor gene mutation status unknown non-small cell lung cancerThorac Cancer201451495410.1111/1759-7714.12074470432626766992Open DOISearch in Google Scholar

Zwitter M, Stanič K, Rajer M, Kern I, Vrankar M, Edelbaher N, et al. Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations. Radiol Oncol 2014; 48: 361-8. 10.2478/raon-2014-0038ZwitterMStaničKRajerMKernIVrankarMEdelbaherNIntercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutationsRadiol Oncol201448361810.2478/raon-2014-0038423055625435849Open DOISearch in Google Scholar

Yoshimura N, Kudoh S, Mitsuoka S, Yoshimoto N, Oka T, Nakai T, et al. Phase II study of a combination regimen of gefitinib and pemetrexed as first-line treatment in patients with non-small cell lung cancer harbouring a sensitive EGFR mutation. Lung Cancer 2015; 90: 65-70. 10.1016/j.lungcan.2015.06.002YoshimuraNKudohSMitsuokaSYoshimotoNOkaTNakaiTPhase II study of a combination regimen of gefitinib and pemetrexed as first-line treatment in patients with non-small cell lung cancer harbouring a sensitive EGFR mutationLung Cancer201590657010.1016/j.lungcan.2015.06.00226238424Open DOISearch in Google Scholar

Yu S, Zhang B, Xiang C, Shu Y, Wu H, Huang X, et al. Prospective assessment of pemetrexed or pemetrexed plus platinum in combination with gefitinib or erlotinib in patients with acquired resistance to gefitinib or erlotinib: a phase II exploratory and preliminary study. Clin Lung Cancer 2015; 16: 121-27. 10.1016/j.cllc.2014.09.007YuSZhangBXiangCShuYWuHHuangXProspective assessment of pemetrexed or pemetrexed plus platinum in combination with gefitinib or erlotinib in patients with acquired resistance to gefitinib or erlotinib: a phase II exploratory and preliminary studyClin Lung Cancer2015161212710.1016/j.cllc.2014.09.00725450874Open DOISearch in Google Scholar

Zwitter M, Rajer M, Stanic K, Vrankar M, Doma A, Cuderman A, et al. Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations. Cancer Biol Ther 2016; 17: 833-9. 10.1080/15384047.2016.1195049ZwitterMRajerMStanicKVrankarMDomaACudermanAIntercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutationsCancer Biol Ther201617833910.1080/15384047.2016.1195049507444727261103Open DOISearch in Google Scholar

Chen YM, Lai CH, Chang HC, Chao TY, Tseng CC, Fang WF, et al. The impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitors. Lung Cancer 2016; 93: 47-54. 10.1016/j.lungcan.2016.01.001ChenYMLaiCHChangHCChaoTYTsengCCFangWFThe impact of clinical parameters on progression-free survival of non-small cell lung cancer patients harboring EGFR-mutations receiving first-line EGFR-tyrosine kinase inhibitorsLung Cancer201693475410.1016/j.lungcan.2016.01.00126898614Open DOISearch in Google Scholar

De Grève J, Van Meerbeeck J, Vansteenkiste JF, Decoster L, Meert AP, Vuylsteke P, et al. Prospective evaluation of first-line erlotinib in advanced non-small cell lung cancer (NSCLC) carrying an activating EGFR mutation: A multicenter academic phase II study in Caucasian patients (FIELT). PLoS One 2016; 11: e0147599. 10.1371/journal.pone.0147599De GrèveJVan MeerbeeckJVansteenkisteJFDecosterLMeertAPVuylstekePProspective evaluation of first-line erlotinib in advanced non-small cell lung cancer (NSCLC) carrying an activating EGFR mutation: A multicenter academic phase II study in Caucasian patients (FIELT)PLoS One201611e014759910.1371/journal.pone.0147599481644727032107Open DOISearch in Google Scholar

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer 2014; 110: 55-62. 10.1038/bjc.2013.721DouillardJYOstorosGCoboMCiuleanuTMcCormackRWebsterAFirst-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm studyBr J Cancer2014110556210.1038/bjc.2013.721388730924263064Open DOISearch in Google Scholar

Inoue A, Yoshida K, Morita S, Imamura F, Seto T, Okamoto I, et al. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 2016; 46: 462-7. 10.1093/jjco/hyw014InoueAYoshidaKMoritaSImamuraFSetoTOkamotoICharacteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patientsJpn J Clin Oncol201646462710.1093/jjco/hyw014487447026977054Open DOISearch in Google Scholar

Rossi A. Chemotherapy plus intercalated or continuous EGFR-TKI in advanced non-small cell lung cancer. Transl Cancer Res 2016; 5(Suppl 4): S659-63.RossiAChemotherapy plus intercalated or continuous EGFR-TKI in advanced non-small cell lung cancerTransl Cancer Res20165(Suppl 4)S6596310.21037/tcr.2016.10.80Search in Google Scholar

Lopes G, Tan PS, Acharyya S, Bilger M, Haaland B. Network meta-analysis comparing first-line therapies and maintenance regimens in EGFR mutated advanced non-small-cell lung cancer (NSCLC). [abstract]. J Clin Oncol 2016; 34(Suppl): abstr e20570.LopesGTanPSAcharyyaSBilgerMHaalandBNetwork meta-analysis comparing first-line therapies and maintenance regimens in EGFR mutated advanced non-small-cell lung cancer (NSCLC). [abstract]J Clin Oncol201634(Suppl): abstre2057010.1200/JCO.2016.34.15_suppl.e20570Search in Google Scholar

Sacher AG, Komatsubara KM, Oxnard GR. Application of plasma genotyping technologies in non-small cell lung cancer: a practical review. J Thorac Oncol 2017; [Epub ahead of print]. 10.1016/j.jtho.2017.05.022SacherAGKomatsubaraKMOxnardGRApplication of plasma genotyping technologies in non-small cell lung cancer: a practical reviewJ Thorac Oncol2017[Epub ahead of print]10.1016/j.jtho.2017.05.02228611011Open DOISearch in Google Scholar

Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. Osmertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 2016; 376: 629-40. 10.1056NEJMMoa1612674MokTSWuY-LAhnM-JGarassinoMCKimHRRamalingamSSOsmertinib or platinum-pemetrexed in EGFR T790M-positive lung cancerN Engl J Med20163766294010.1056NEJMMoa1612674Open DOISearch in Google Scholar

Sugawara S, Oizumi S, Minato K, Harada T, Inoue A, Fujita Y et al. Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902. Ann Oncol 2015; 26: 888-94. 10.1093/annonc/mdv063SugawaraSOizumiSMinatoKHaradaTInoueAFujitaYRandomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902Ann Oncol2015268889410.1093/annonc/mdv063Open DOISearch in Google Scholar

Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, et al. Randomized Phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol 2016; 34: 3258-66. 10.1200/JCO.2016.66.9218ChengYMurakamiHYangPCHeJNakagawaKKangJHRandomized Phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutationsJ Clin Oncol20163432586610.1200/JCO.2016.66.9218Open DOISearch in Google Scholar

Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014; 15: 1236-44. 10.1016/S1470-2045(14)70381-XSetoTKatoTNishioMGotoKAtagiSHosomiYErlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 studyLancet Oncol20141512364410.1016/S1470-2045(14)70381-XOpen DOISearch in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo