A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)

Blumenschein, G.R.; Smit, E.F.; Planchard, D.; Kim, D.-W.; Cadranel, J.; De Pas, T.; Dunphy, F.; Udud, K.; Ahn, M.-J.; Hanna, N.H.; Kim, J.-H.; Mazieres, J.; Kim, S.-W.; Baas, P.; Rappold, E.; Redhu, S.; Puski, A.; Wu, F.S.; Jänne, P.A.

doi:10.1093/annonc/mdv072

Cited by 351Lung Cancer Treatments and MutationsLung Cancer Research StudiesLung Cancer Diagnosis and Treatment

A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)

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Blumenschein, G.R., Smit, E.F., Planchard, D., Kim, D.-W., Cadranel, J., De Pas, T., Dunphy, F., Udud, K. +11 more·2015·Annals of Oncology

DOI 10.1093/annonc/mdv072PMC PMC4855243

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Abstract

Background KRAS mutations are detected in 25% of non-small-cell lung cancer (NSCLC) and no targeted therapies are approved for this subset population. Trametinib, a selective allosteric inhibitor of MEK1/MEK2, demonstrated preclinical and clinical activity in KRAS-mutant NSCLC. We report a phase II trial comparing trametinib with docetaxel in patients with advanced KRAS-mutant NSCLC.Patients and methods Eligible patients with histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy were randomly assigned in a ratio of 2 : 1 to trametinib (2 mg orally once daily) or docetaxel (75 mg/m(2) i.v. every 3 weeks). Crossover to the other arm after disease progression was allowed. Primary end point was progression-free survival (PFS). The study was prematurely terminated after the interim analysis of 92 PFS events, which showed the comparison of trametinib versus docetaxel for PFS crossed the futility boundary.Results One hundred and twenty-nine patients with KRAS-mutant NSCLC were randomized; of which, 86 patients received trametinib and 43 received docetaxel. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (hazard ratio [HR] 1.14; 95% CI 0.75-1.75; P = 0.5197). Median overall survival, while the data are immature, was 8 months in the trametinib arm and was not reached in the docetaxel arm (HR 0.97; 95% CI 0.52-1.83; P = 0.934). There were 10 (12%) partial responses (PRs) in the trametinib arm and 5 (12%) PRs in the docetaxel arm (P = 1.0000). The most frequent adverse events (AEs) in ≥20% of trametinib patients were rash, diarrhea, nausea, vomiting, and fatigue. The most frequent grade 3 treatment-related AEs in the trametinib arm were hypertension, rash, diarrhea, and asthenia.Conclusion Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC.Clinicaltrialsgov registration number NCT01362296.

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Due to resistance acquisition, MEK inhibitors have shown limited benefit as monotherapy in KRAS mutant CRC.
“However, due to resistance acquisition, MEK inhibitors have shown limited benefit as monotherapy in KRAS mutant CRC [73,74].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [74]
Kinase inhibitors targeting molecules downstream of KRAS-like MEK inhibitors have shown modest efficacy, with response rates of 11% for selumetinib and 12% for trametinib.
“Kinase inhibitors targeting molecules downstream of KRAS-like MEK inhibitors have shown modest efficacy, with response rates of 11% for selumetinib 16 and 12% for trametinib.17”
From K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways (2019) · cites this paper as [17]
In a phase II trial, trametinib as monotherapy showed response rate and PFS similar to docetaxel in previously treated KRAS-mutant NSCLC.
“In a phase II trial, trametinib as a monotherapy showed RR and PFS similar to docetaxel in previously treated KRAS-mutant NSCLC (49).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [49]

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Judd, J., Karim, N. A., Khan, H., Naqash, A. R., Baca, Y., Xiu, J., VanderWalde, A. M., Mamdani, H. M., Raez, L. E., Nagasaka, M., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0201 · Cited by 209 · see citing works
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Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer
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Current Landscape of Targeted Therapy in Lung Cancer
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Trametinib: a MEK inhibitor for management of metastatic melanoma
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KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer
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The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC)
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Drugging KRAS: Current perspectives and state-of-art review
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Exploiting the therapeutic implications of KRAS inhibition on tumor immunity
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BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers
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Circulating tumour DNA sequence analysis as an alternative to multiple myeloma bone marrow aspirates
Kis, O., Kaedbey, R., Chow, S., Danesh, A., Dowar, M., Li, T., Li, Z., Liu, J., Mansour, M., Masih‐Khan, E., et al. (2017) · Nature Communications · doi:10.1038/ncomms15086 · Cited by 137 · see citing works
Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future
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New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness
Yang, H., Liang, S.-Q., Schmid, R. A., & Peng, R.-W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00953 · Cited by 129 · see citing works
MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival
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Targeting RAS-mutant cancers: is ERK the key?
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ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition
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Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C–Mutant Non–Small Cell Lung Cancer
Arbour, K. C., Rizvi, H. A., Plodkowski, A. J., Hellmann, M. D., Knežević, A., Heller, G., Yu, H. A., Ladanyi, M., Kris, M. G., Arcila, M. E., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4023 · Cited by 129 · see citing works
Current therapy of KRAS-mutant lung cancer
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Mechanisms of Resistance to KRASG12C Inhibitors
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RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms
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Targeted Therapies in Non-Small Cell Lung Cancer—Beyond EGFR and ALK
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Bax/Bcl-2 Cascade Is Regulated by the EGFR Pathway: Therapeutic Targeting of Non-Small Cell Lung Cancer
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Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers
Ozkan‐Dagliyan, I., Diehl, J. N., George, S. D., Schaefer, A., Papke, B., Klotz‐Noack, K., Waters, A. M., Goodwin, C. M., Gautam, P., Pierobon, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107764 · Cited by 102 · see citing works
Real-World Evidence In Support Of Precision Medicine: Clinico-Genomic Cancer Data As A Case Study
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Trametinib for progressive pediatric low-grade gliomas
Kondyli, M., Larouche, V., Saint‐Martin, C., Ellezam, B., Pouliot, L., Sinnett, D., Legault, G., Crevier, L., Weil, A. G., Farmer, J., et al. (2018) · Journal of Neuro-Oncology · doi:10.1007/s11060-018-2971-9 · Cited by 104 · see citing works
Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia
Erba, H. P., Becker, P. S., Shami, P. J., Grunwald, M. R., Flesher, D., Zhu, M., Rasmussen, E., Henary, H. A., Anderson, A., & Wang, E. S. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019030916 · Cited by 103 · see citing works
Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment
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Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary
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Breakthrough in targeted therapy for non-small cell lung cancer
Zhencong, Y., Huang, Y., Ke, J., Zhu, X. M., Leng, S., & Luo, H. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111079 · Cited by 95 · see citing works
SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Lu, H., Liu, C., Velazquez, R., Wang, H., Dunkl, L. M., Kazic-Legueux, M., Haberkorn, A., Billy, E., Manchado, E., Brachmann, S. M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0852 · Cited by 90 · see citing works
BRAF and MEK Inhibitors and Their Toxicities: A Meta-Analysis
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Relationship between Progression-free Survival and Overall Survival in Randomized Clinical Trials of Targeted and Biologic Agents in Oncology
Hess, L. M., Brnabic, A. J. M., Mason, O., Lee, P., & Barker, S. S. (2019) · Journal of Cancer · doi:10.7150/jca.32205 · Cited by 93 · see citing works
Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS -Mutant Non–Small Cell Lung Cancer
Nangia, V., Siddiqui, F. M., Caenepeel, S., Timonina, D., Bilton, S. J., Phan, N., Gomez-Caraballo, M., Archibald, H. L., Li, C., Fraser, C., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0277 · Cited by 94 · see citing works
Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers
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LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors
Monaco, K., Delach, S. M., Yuan, J., Mishina, Y. M., Fordjour, P., Labrot, E., McKay, D., Guo, R., Higgins, S., Wang, H. Q., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2563 · Cited by 88 · see citing works
Actionable gene-based classification toward precision medicine in gastric cancer
Ichikawa, H., Nagahashi, M., Shimada, Y., Hanyu, T., Ishikawa, T., Kameyama, H., Kobayashi, T., Sakata, J., Yabusaki, H., Nakagawa, S., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0484-3 · Cited by 87 · see citing works
An Immunogenic Model of KRAS-Mutant Lung Cancer Enables Evaluation of Targeted Therapy and Immunotherapy Combinations
Boumelha, J., Trécesson, S. D. C., Law, E. K., Romero-Clavijo, P., Coelho, M. A., Ng, K. W., Mugarza, E., Moore, C., Rana, S., Caswell, D. R., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0325 · Cited by 84 · see citing works
KRAS G12C Mutations in NSCLC: From Target to Resistance
Addeo, A., Banna, G. L., & Friedlaender, A. (2021) · Cancers · doi:10.3390/cancers13112541 · Cited by 84 · see citing works
Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity
Matikas, A., Mistriotis, D., Georgoulias, V., & Kotsakis, A. P. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.12.005 · Cited by 82 · see citing works
Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1
Xie, J., Xia, L., Xiang, W. D., He, W., Yin, H., Wang, F., Gao, T., Qi, W., Yang, Z., Yang, X., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1918845117 · Cited by 84 · see citing works
Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma
Manoharan, N., Choi, J. J., Chordas, C. A., Zimmerman, M. A., Scully, J., Clymer, J. R., Filbin, M. G., Ullrich, N. J., Bandopadhayay, P., Chi, S. N., et al. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03592-8 · Cited by 82 · see citing works
The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction
Klomp, J. E., Klomp, J. A., & Der, C. J. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200507 · Cited by 83 · see citing works
Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials
Huang, Q., Zhang, H., Hai, J., Socinski, M. A., Lim, E. K. S., Chen, H., & Stebbing, J. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1396403 · Cited by 82 · see citing works
Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges
Tang, D., Kroemer, G., & Kang, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01422-7 · Cited by 80 · see citing works
The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer
Lee, J. W., Zhang, Y. X., Eoh, K. J., Sharma, R., Sanmamed, M. F., Wu, J. Q., Choi, J., Park, H. S., Iwasaki, A., Kaftan, E. J., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.02.004 · Cited by 80 · see citing works
The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth
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Intermittent schedules of the oral RAF–MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study
Guo, C., Chénard-Poirier, M., Roda, D., de Miguel, M., Harris, S. J., Candilejo, I. M., Sriskandarajah, P., Xu, W., Scaranti, M., Constantinidou, A., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30464-2 · Cited by 78 · see citing works
KRAS Inhibitors– yes but what next? Direct targeting of KRAS– vaccines, adoptive T cell therapy and beyond
Nagasaka, M., Potugari, B. R., Nguyen, A., Sukari, A. W., Azmi, A. S., & Ou, S. I. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102309 · Cited by 78 · see citing works
MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer
Casacuberta‐Serra, S., González-Larreategui, Í., Capitán-Leo, D., & Soucek, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01907-z · Cited by 80 · see citing works
Therapeutics Targeting Mutant KRAS
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Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant Melanomas
Dankner, M., Lajoie, M., Moldoveanu, D., Nguyen, T.-T., Savage, P., Rajkumar, S., Huang, X., Lvova, M., Protopopov, A. I., Vuzman, D., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3384 · Cited by 75 · see citing works
KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup
Xie, M., Xu, X., & Fan, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.672612 · Cited by 76 · see citing works
MEK inhibitors under development for treatment of non-small-cell lung cancer
Kim, C. G., & Giaccone, G. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1415324 · Cited by 73 · see citing works
Relationship between Overall Survival and Response or Progression-Free Survival in Advanced Non–Small Cell Lung Cancer Patients Treated with Anti–PD-1/PD-L1 Antibodies
Shukuya, T., Mori, K. P., Amann, J. M., Bertino, E. M., Otterson, G. A., Shields, P. G., Morita, S., & Carbone, D. P. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.07.017 · Cited by 74 · see citing works
Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers
Peng, D. H., Rodriguez, B. L., Diao, L., Gaudreau, P.-O., Padhye, A., Konen, J. M., Ochieng, J. K., Class, C. A., Fradette, J. J., Gibson, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22875-w · Cited by 72 · see citing works
Drugging the Undruggable: Advances on RAS Targeting in Cancer
Molina‐Arcas, M., Samani, A., & Downward, J. (2021) · Genes · doi:10.3390/genes12060899 · Cited by 73 · see citing works
Comprehensive pancancer genomic analysis reveals (RTK)-RAS-RAF-MEK as a key dysregulated pathway in cancer: Its clinical implications
Imperial, R. J. L., Toor, O. M., Hussain, A., Subramanian, J., & Masood, A. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.016 · Cited by 71 · see citing works
Assessing Therapeutic Efficacy of MEK Inhibition in a KRASG12C-Driven Mouse Model of Lung Cancer
Li, S., Liu, S., Deng, J., Akbay, E. A., Hai, J., Ambrogio, C., Zhang, L., Zhou, F., Jenkins, R. W., Adeegbe, D. O., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3438 · Cited by 67 · see citing works
Comprehensive Clinical and Molecular Characterization of KRASG12C-Mutant Colorectal Cancer
Henry, J. T., Coker, O., Chowdhury, S., Shen, J. P., Morris, V. K., Dasari, A., Raghav, K., Nusrat, M., Kee, B., Parseghian, C., et al. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00256 · Cited by 66 · see citing works
A systematic review of targeted agents for non-small cell lung cancer
Vestergaard, H. H., Christensen, M. R., & Lassen, U. (2017) · Acta Oncologica · doi:10.1080/0284186x.2017.1404634 · Cited by 66 · see citing works
MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically
Munkhbaatar, E., Dietzen, M., Agrawal, D., Anton, M., Jesinghaus, M., Boxberg, M., Pfarr, N., Bidola, P., Uhrig, S., Höckendorf, U., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18372-1 · Cited by 66 · see citing works
Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation
Brubaker, D. K., Paulo, J. A., Sheth, S., Poulin, E. J., Popow, O., Joughin, B. A., Strasser, S. D., Starchenko, A., Gygi, S. P., Lauffenburger, D. A., et al. (2019) · Cell Systems · doi:10.1016/j.cels.2019.07.006 · Cited by 57 · see citing works
“However, because activated KRAS engages multiple downstream pathways, single agents targeting canonical effectors are not clinically effective (Blumenschein et al., 2015).”
Background
Implications of KRAS mutations in acquired resistance to treatment in NSCLC
Re, M. D., Rofi, E., Restante, G., Crucitta, S., Arrigoni, E., Fogli, S., Maïo, M. D., Petrini, I., & Danesi, R. (2017) · Oncotarget · doi:10.18632/oncotarget.23553 · Cited by 62 · see citing works
A state-of-the-art review of stratified medicine in cancer: towards a future precision medicine strategy in cancer
Middleton, G., Robbins, H. L., André, F., & Swanton, C. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.11.004 · Cited by 58 · see citing works
Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer
Dolly, S. O., Collins, D. C., Sundar, R., Popat, S., & Yap, T. A. (2017) · Drugs · doi:10.1007/s40265-017-0732-2 · Cited by 57 · see citing works
HSP90/AXL/eIF4E-regulated unfolded protein response as an acquired vulnerability in drug-resistant KRAS-mutant lung cancer
Yang, H., Liang, S.-Q., Xu, D., Yang, Z., Marti, T. M., Gao, Y., Kocher, G. J., Zhao, H., Schmid, R. A., & Peng, R.-W. (2019) · Oncogenesis · doi:10.1038/s41389-019-0158-7 · Cited by 58 · see citing works
ZEB1 suppression sensitizes KRAS mutant cancers to MEK inhibition by an IL17RD-dependent mechanism
Peng, D. H., Kundu, S. T., Fradette, J. J., Diao, L., Tong, P., Byers, L. A., Wang, J., Canales, J. R., Villalobos, P. A., Mino, B., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1238 · Cited by 53 · see citing works
FUBP1 promotes colorectal cancer stemness and metastasis via DVL1‐mediated activation of Wnt/β‐catenin signaling
Yin, H., Gao, T., Xie, J., Huang, Z., Zhang, X., Yang, F., Qi, W., Yang, Z., Zhou, T., Gao, G., et al. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13064 · Cited by 57 · see citing works
The MEK/ERK/miR-21 Signaling Is Critical in Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Cancer Cells
Huang, W.-C., Yadav, V. K., Cheng, W.-H., Wang, C., Hsieh, M., Huang, T., Lin, S., Yeh, C., & Kuo, K.-T. (2021) · Cancers · doi:10.3390/cancers13236005 · Cited by 55 · see citing works
Targeting KRAS-Mutant Non–Small-Cell Lung Cancer: One Mutation at a Time, With a Focus on KRAS G12C Mutations
Burns, T. F., Borghaei, H., Ramalingam, S. S., Mok, T. S. K., & Peters, S. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00744 · Cited by 56 · see citing works
Histone Deacetylase Inhibition Enhances the Antitumor Activity of a MEK Inhibitor in Lung Cancer Cells Harboring RAS Mutations
Yamada, T., Amann, J. M., Tanimoto, A., Taniguchi, H., Shukuya, T., Timmers, C., Yano, S., Shilo, K., & Carbone, D. P. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0146 · Cited by 44 · see citing works

Oral MEK1/MEK2 inhibitor trametinib (GSK1120212) in combination with docetaxel in KRAS-mutant and wild-type (WT) advanced non-small cell lung cancer (NSCLC): A phase I/Ib trial.
Gandara, D. R., Hiret, S., Blumenschein, G. R., Barlési, F., Delord, J., Madelaine, J., Infante, J. R., Reckamp, K. L., Lara, P. N., Audebert, C., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.8028 · Cited by 27 · see citing works
Self-citation
MEK114653: A randomized, multicenter, phase II study to assess efficacy and safety of trametinib (T) compared with docetaxel (D) in KRAS-mutant advanced non–small cell lung cancer (NSCLC).
Blumenschein, G. R., Smit, E. F., Planchard, D., Kim, D., Cadranel, J. L., Pas, T. M. D., Dunphy, F., Udud, K., Ahn, M., Hanna, N. H., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.8029 · Cited by 21 · see citing works
Self-citation
S1507: Phase II study of docetaxel and trametinib in patients with G12C or non-G12C KRAS mutation positive (+) recurrent non-small cell lung cancer (NSCLC).
Gadgeel, S. M., Miao, J., Riess, J. W., Mack, P. C., Gerstner, G. J., Burns, T. F., Taj, A., Akerley, W. L., Dragnev, K. H., Moon, J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.9021 · Cited by 15 · see citing works
A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non–Small Cell Lung Cancer
Gandara, D. R., Leighl, N. B., Delord, J., Barlési, F., Bennouna, J., Zalcman, G., Infante, J. R., Reckamp, K. L., Kelly, K. L., Shepherd, F. A., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.11.2218 · Cited by 49 · see citing works
Self-citation
Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study
Jänne, P. A., Shaw, A. T., Pereira, J. R., Jeannin, G., Vansteenkiste, J., Barrios, C., Franke, F. A., Grinsted, L., Zazulina, V., Smith, P., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70489-8 · Cited by 655 · see citing works

Authors: Blumenschein, G. R., Smit, E. F., Planchard, D., Kim, D.-W., Cadranel, J., De Pas, T., Dunphy, F., Udud, K., Ahn, M.-J., Hanna, N. H., Kim, J.-H., Mazieres, J., Kim, S.-W., Baas, P., Rappold, E., Redhu, S., Puski, A., Wu, F. S., & Jänne, P. A.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Vrije Universiteit Amsterdam (NL)
Institut Gustave Roussy (FR)
Seoul National University (KR)
Assistance Publique – Hôpitaux de Paris (FR)
Duke Medical Center (US)
Országos Korányi Tbc és Pulmonológiai Intézet (HU)
Samsung Medical Center (KR)
Indiana University Health (US)
Yonsei University (KR)
Asan Medical Center (KR)
The Netherlands Cancer Institute (NL)
GlaxoSmithKline (United States) (US)
Corresponding author: Blumenschein, G.R.
ORCID: Blumenschein, G.R.
Smit, E.F.
Planchard, D.
Cadranel, J.
Ahn, M.-J.
Hanna, N.H.
Kim, J.-H.
Kim, S.-W.
Wu, F.S.
Venue: Annals of Oncology
Publisher: Elsevier BV
Published: 2015-05
Volume: 26
Issue: 5
Pages: 894-901
ISSN: 0923-7534 (ISSN-L)
DOI: 10.1093/annonc/mdv072
PMC: PMC4855243
OpenAlex: W2160586729
Cited by: 349
References: 30
Citations by year: 2026: 10 · 2025: 21 · 2024: 39 · 2023: 28 · 2022: 40 · 2021: 53 · 2020: 35 · 2019: 33 · 2018: 29 · 2017: 28 · 2016: 16 · 2015: 15 · 2014: 1
FWCI: 23.47
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1651 d)
Locations: Annals of Oncology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Seoul National University Open Repository (Seoul National University) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: GlaxoSmithKline (NCT01362296)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: trametinib, docetaxel, KRAS-mutant non-small cell lung cancer, targeted therapy, progression-free survival, overall survival, futility boundaries, EGFR wild-type, EGFR tyrosine kinase inhibitors
MeSH terms: Docetaxel, Adult, Aged, Antineoplastic Agents, Phytogenic, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Pyridones, Pyrimidinones, Time Factors, Biomarkers, Tumor, Signal Transduction, Proto-Oncogene Proteins p21(ras), Treatment Outcome, Disease Progression, Disease-Free Survival, Taxoids, Protein Kinase Inhibitors, MAP Kinase Kinase 1, MAP Kinase Kinase 2, Kaplan-Meier Estimate

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A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)

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