Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study
Abstract
Background No targeted therapies are available for KRAS-mutant non-small-cell lung cancer (NSCLC). Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence of synergistic activity with docetaxel in KRAS-mutant cancers. We did a prospective, randomised, phase 2 trial to assess selumetinib plus docetaxel in previously treated patients with advanced KRAS-mutant NSCLC.Methods Eligible patients were older than 18 years of age; had histologically or cytologically confirmed stage IIIB-IV KRAS-mutant NSCLC; had failed first-line therapy for advanced NSCLC; had WHO performance status of 0-1; had not received previous therapy with either a MEK inhibitor or docetaxel; and had adequate bone marrow, renal, and liver function. Patients were randomly assigned (in a 1:1 ratio) to either oral selumetinib (75 mg twice daily in a 21 day cycle) or placebo; all patients received intravenous docetaxel (75 mg/m(2) on day 1 of a 21 day cycle). Randomisation was done with an interactive voice response system and investigators, patients, data analysts, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival, analysed for all patients with confirmed KRAS mutations. This study is registered with ClinicalTrials.gov, number NCT00890825.Findings Between April 20, 2009, and June 30, 2010, we randomly assigned 44 patients to receive selumetinib and docetaxel (selumetinib group) and 43 to receive placebo and docetaxel (placebo group). Of these, one patient in the selumetinib group and three in the placebo group were excluded from efficacy analyses because their tumours were not confirmed to be KRAS-mutation positive. Median overall survival was 9·4 months (6·8-13·6) in the selumetinib group and 5·2 months (95% CI 3·8-non-calculable) in the placebo group (hazard ratio [HR] for death 0·80, 80% CI 0·56-1·14; one-sided p=0·21). Median progression-free survival was 5·3 months (4·6-6·4) in the selumetinib group and 2·1 months (95% CI 1·4-3·7) in the placebo group (HR for progression 0·58, 80% CI 0·42-0·79; one-sided p=0·014). 16 (37%) patients in the selumetinib group and none in the placebo group had an objective response (p<0·0001). Adverse events of grade 3 or higher occurred in 36 (82%) patients in the selumetinib group and 28 (67%) patients in the placebo group. The most common grade 3-4 adverse events were neutropenia (29 [67%] of 43 patients in the selumetinib group vs 23 [55%] of 42 patients in the placebo group), febrile neutropenia (eight [18%] of 44 patients in the selumetinib group vs none in the placebo group), dyspnoea (one [2%] of 44 patients in the selumetinib group vs five [12%] of 42 in the placebo group), and asthenia (four [9%] of 44 patients in the selumetinib group vs none in the placebo group).Interpretation Selumetinib plus docetaxel has promising efficacy, albeit with a higher number of adverse events than with docetaxel alone, in previously treated advanced KRAS-mutant NSCLC. These findings warrant further clinical investigation of selumetinib plus docetaxel in KRAS-mutant NSCLC.Funding AstraZeneca.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the phase II trial, median PFS was significantly improved in patients receiving selumetinib (5.3 vs 2.1 months; HR 0.58, 80% CI 0.42-0.79; one-sided p=0.014).
“The median PFS was significantly improved in patients receiving selumetinib (5.3 vs. 2.1 months; HR for progression 0·58, 80% CI 0·42–0·79; one-sided p = 0·014)”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [47]
In the phase II trial, response rate was 37% vs 0% (p<0.0001).
“as was the response rate (37% vs. 0%; p < 0·0001).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [47]
Cites
Jemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 54,708 · see citing works
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Mok, T. S., Wu, Y.-L., Thongprasert, S., Yang, C.-H., Chu, D.-T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810699 · Cited by 8,261 · see citing works
Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., Palmero, R., Garcia-Gomez, R., Pallares, C., Sanchez, J. M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70393-x · Cited by 5,489 · see citing works
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061 · see citing works
Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer
Schiller, J. H., Harrington, D., Belani, C. P., Langer, C., Sandler, A., Krook, J., Zhu, J., & Johnson, D. H. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa011954 · Cited by 4,955 · see citing works
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Kwak, E. L., Bang, Y., Camidge, D. R., Shaw, A. T., Solomon, B., Maki, R. G., Ou, S. I., Dezube, B. J., Janne, P. A., Costa, D. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1006448 · Cited by 4,442 · see citing works
Self-citationCOMPARISON OF FOUR CHEMOTHERAPY REGIMENS FOR ADVANCED NON-SMALL-CELL LUNG CANCER
Chiller, J. O. H. S., Arrington, D. A. H., Elani, C. H. P. B., Anger, C., Andler, A. L. S., Rook, J. A. K., Hu, J., & Ohnson, D. A. H. J. (2002) · Cited by 3,730 · see citing works
Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)
Newton, C. R., Graham, A., Heptinstall, L., Powell, S. J., Summers, C. W., Kalsheker, N. A., Smith, J. C., & Markham, A. F. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.7.2503 · Cited by 2,476 · see citing works
Hanna, N., Shepherd, F. A., Fossella, F. V., Pereira, J. R., De Marinis, F., von Pawel, J., Gatzemeier, U., Tsao, T. C. Y., Pless, M., Muller, T., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.163 · Cited by 2,426 · see citing works
Self-citationShepherd, F. A., Dancey, J. E., Ramlau, R., Mattson, K. V., Gralla, R. J., O’Rourke, M. A., Levitan, N. I., Gressot, L., Vincent, M. D., Burkes, R. L., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.10.2095 · Cited by 2,178 · see citing works
Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer
Winton, T. L., Livingston, R. B., Johnson, D. H., Rigas, J. R., Johnston, M., Butts, C. A., Cormier, Y. F., Goss, G., Inculet, R., Vallières, E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043623 · Cited by 1,810 · see citing works
Brady, M. J., Cella, D. F., Mo, F., Bonomi, A. E., Tulsky, D. S., Lloyd, S. R., Deasy, S., Cobleigh, M., & Shiomoto, G. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.3.974 · Cited by 1,752 · see citing works
Smith, T. J., Khatcheressian, J. L., Lyman, G. H., Ozer, H., Armitage, J. O., Balducci, L., Bennett, C. L., Cantor, S. B., Crawford, J., Cross, S. J., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.4451 · Cited by 1,634 · see citing works
Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S., Herbst, R. S., Ince, W. L., Janne, P. A., Januario, T., Johnson, D. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.857 · Cited by 1,453 · see citing works
A Confidence Interval for the Median Survival Time
Brookmeyer, R., & Crowley, J. (1982) · Biometrics · doi:10.2307/2530286 · Cited by 914 · see citing works
Cella, D. F., Bonomi, A. E., Lloyd, S. R., Tulsky, D. S., Kaplan, E. J., & Bonomi, P. (1995) · Lung Cancer · doi:10.1016/0169-5002(95)00450-f · Cited by 750 · see citing works
Mitsudomi, T., & Yatabe, Y. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00607.x · Cited by 606 · see citing works
Mascaux, C., Iannino, N., Martin, B., Paesmans, M., Berghmans, T., Dusart, M., Haller, A., Lothaire, P., Meert, A.-P., Noël, S., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602258 · Cited by 604 · see citing works
Yeh, T. C., Marsh, V., Bernat, B. A., Ballard, J., Colwell, H., Evans, R. J., Parry, J., Smith, D. J., Brandhuber, B. J., Gross, S. D., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1150 · Cited by 583 · see citing works
Adjei, A. A., Cohen, R. B., Franklin, W. A., Morris, C. D., Wilson, D. M., Molina, J. R., Hanson, L. J., Gore, L., Chow, L. Q. M., Leong, S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.4956 · Cited by 568 · see citing works
Crinò, L., Weder, W., van Meerbeeck, J. P., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq207 · Cited by 539 · see citing works
Self-citationDouillard, J.-Y., Shepherd, F. A., Hirsh, V., Mok, T., Socinski, M. A., Gervais, R., Liao, M.-L., Bischoff, H., Reck, M., Sellers, M. V., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.3030 · Cited by 492 · see citing works
A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
Chen, Z., Cheng, K., Walton, Z., Wang, Y., Ebi, H., Shimamura, T., Liu, Y., Tupper, T., Ouyang, J., Li, J., et al. (2012) · Nature · doi:10.1038/nature10937 · Cited by 446 · see citing works
Santos, E., Martin-Zanca, D., Reddy, E. P., Pierotti, M. A., Della Porta, G., & Barbacid, M. (1984) · Science · doi:10.1126/science.6695174 · Cited by 418 · see citing works
Herbst, R. S., Sun, Y. P., Eberhardt, W., Germonpré, P. R., Saijo, N., Zhou, C., Wang, J., Li, L., Kabbinavar, F. F., Ichinose, Y., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70132-7 · Cited by 414 · see citing works
Davies, B. R., Logié, A., McKay, J. S., Martin, P. D., Steele, S. J., Jenkins, R., Cockerill, M. J., Cartlidge, S., & Smith, P. D. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0231 · Cited by 388 · see citing works
Self-citationBodoky, G., Timcheva, C., Spigel, D. R., La Stella, P. J., Ciuleanu, T. E., Pover, G., & Tebbutt, N. C. (2012) · Investigational New Drugs · doi:10.1007/s10637-011-9687-4 · Cited by 236 · see citing works
Banerji, U., Camidge, D. R., Verheul, H. M. W., Agarwal, R., Sarker, D., Kaye, S. B., Desar, I. M. E., Timmer-Bonte, J. N. H., Eckhardt, S., Lewis, K. D., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2483 · Cited by 212 · see citing works
Self-citationHainsworth, J. D., Cebotaru, C. L., Kanarev, V., Ciuleanu, T., Damyanov, D., Stella, P. J., Ganchev, H., Pover, G. M., Morris, C. D., & Tzekova, V. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181e8b3a3 · Cited by 162 · see citing works
Bennouna, J., Láng, I., Valladares‐Ayerbes, M., Boér, K., Adenis, A., Escudero, P., Kim, T. Y., Pover, G. M., Morris, C. D., & Douillard, J.-Y. (2010) · Investigational New Drugs · doi:10.1007/s10637-010-9392-8 · Cited by 141 · see citing works
Reddy, B., Engle, A., Katsifis, S., et al. (1989) · PubMed · Cited by 129 · see citing works
Holt, S. V., Logié, A., Odedra, R., Heier, A., Heaton, S. P., Alférez, D., Davies, B. R., Wilkinson, R. W., & Smith, P. D. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.8 · Cited by 112 · see citing works
Self-citationBlumenschein, G. R., Ludwig, C., Thomas, G., Tan, E., Fanucchi, M., Santoro, A., Crawford, J., Breton, J. L., O’Brien, M., & Khuri, F. R. (2005) · Lung Cancer · doi:10.1016/s0169-5002(05)80215-6 · Cited by 24 · see citing works
Kim, K., Infante, J. R., Cohen, R. B., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-11-b225 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Coudray, N., Ocampo, P. S., Sakellaropoulos, T., Narula, N., Snuderl, M., Fenyö, D., Moreira, A. L., Razavian, N., & Tsirigos, A. (2018) · Nature Medicine · doi:10.1038/s41591-018-0177-5 · Cited by 2,930 · see citing works
Targeting RAS–ERK signalling in cancer: promises and challenges
Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163 · see citing works
Skoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936 · see citing works
Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges
Day, C.-P., Merlino, G., & Van Dyke, T. (2015) · Cell · doi:10.1016/j.cell.2015.08.068 · Cited by 676 · see citing works
Jordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643 · see citing works
MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road
Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606 · see citing works
Self-citationThe Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies
Lin, L., Sabnis, A. J., Chan, E., Olivas, V., Cade, L., Pazarentzos, E., Asthana, S., Neel, D., Yan, J. J., Lu, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3218 · Cited by 551 · see citing works
Arbour, K. C., Jordan, E., Kim, H. R., Dienstag, J., Yu, H. A., Sanchez-Vega, F., Lito, P., Berger, M., Solit, D. B., Hellmann, M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1841 · Cited by 466 · see citing works
Genetic alterations defining NSCLC subtypes and their therapeutic implications
Pikor, L. A., Ramnarine, V. R., Lam, S., & Lam, W. L. (2013) · Lung Cancer · doi:10.1016/j.lungcan.2013.07.025 · Cited by 375 · see citing works
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., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv072 · Cited by 349 · see citing works
Targeting KRAS in non-small-cell lung cancer: recent progress and new approaches
Reck, M., Carbone, D. P., Garassino, M., & Barlesi, F. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.06.001 · Cited by 326 · see citing works
Jänne, P. A., van den Heuvel, M. M., Barlesi, F., Cobo, M., Mazieres, J., Crinò, L., Orlov, S., Blackhall, F., Wolf, J., Garrido, P., et al. (2017) · JAMA · doi:10.1001/jama.2017.3438 · Cited by 335 · see citing works
Self-citationKRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target
Román, M., Baraibar, I., López, I., Nadal, E., Rolfo, C., Vicent, S., & Gil-Bazo, I. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0789-x · Cited by 301 · see citing works
Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.045 · Cited by 304 · see citing works
Scientific Advances in Lung Cancer 2015
Tsao, A. S., Scagliotti, G. V., Bunn, P. A., Carbone, D. P., Warren, G. W., Bai, C., de Koning, H. J., Yousaf-Khan, A. U., McWilliams, A., Tsao, M. S., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.03.012 · Cited by 284 · see citing works
Drilon, A., Wang, L., Arcila, M. E., Balasubramanian, S., Greenbowe, J. R., Ross, J. S., Stephens, P., Lipson, D., Miller, V. A., Kris, M. G., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2683 · Cited by 274 · see citing works
KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition
Misale, S., Fatherree, J. P., Cortez, E., Li, C., Bilton, S., Timonina, D., Myers, D. T., Lee, D., Gomez-Caraballo, M., Greenberg, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0368 · Cited by 259 · see citing works
Molecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220 · see citing works
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer
Molina-Arcas, M., Moore, C., Rana, S., van Maldegem, F., Mugarza, E., Romero-Clavijo, P., Herbert, E., Horswell, S., Li, L.-S., Janes, M. R., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw7999 · Cited by 203 · see citing works
Wakimoto, H., Tanaka, S., Curry, W. T., Loebel, F., Zhao, D., Tateishi, K., Chen, J., Klofas, L. K., Lelic, N., Kim, J. C., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3052 · Cited by 190 · see citing works
Gerber, D. E., Camidge, D. R., Morgensztern, D., Cetnar, J., Kelly, R. J., Ramalingam, S. S., Spigel, D. R., Jeong, W., Scaglioni, P. P., Zhang, S., et al. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2019.10.033 · Cited by 167 · see citing works
Prognostic and Predictive Value in<i>KRAS</i>in Non–Small-Cell Lung Cancer: A Review
Wood, K., Hensing, T., Malik, R., & Salgia, R. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.0405 · Cited by 164 · see citing works
Drugging KRAS: Current perspectives and state-of-art review
Parikh, K., Banna, G., Liu, S. V., Friedlaender, A., Desai, A., Subbiah, V., & Addeo, A. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01375-4 · Cited by 164 · see citing works
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
Current therapy of KRAS-mutant lung cancer
Ghimessy, A., Radeczky, P., Laszlo, V., Hegedus, B., Renyi-Vamos, F., Fillinger, J., Klepetko, W., Lang, C., Dome, B., & Megyesfalvi, Z. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09903-9 · Cited by 115 · see citing works
Calles, A., Sholl, L. M., Rodig, S. J., Pelton, A. K., Hornick, J. L., Butaney, M., Lydon, C., Dahlberg, S. E., Oxnard, G. R., Jackman, D. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3112 · Cited by 115 · see citing works
Rekhtman, N., Ang, D. C., Riely, G. J., Ladanyi, M., & Moreira, A. L. (2013) · Modern Pathology · doi:10.1038/modpathol.2013.74 · Cited by 117 · see citing works
A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Vasan, N., Boyer, J. L., & Herbst, R. S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1762 · Cited by 102 · see citing works
KRAS Protein Stability Is Regulated through SMURF2: UBCH5 Complex-Mediated β-TrCP1 Degradation
Shukla, S., Allam, U. S., Ahsan, A., Chen, G., Krishnamurthy, P. M., Marsh, K., Rumschlag, M., Shankar, S., Whitehead, C., Schipper, M., et al. (2014) · Neoplasia · doi:10.1593/neo.14184 · Cited by 96 · see citing works
Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers
Sulahian, R., Kwon, J. J., Walsh, K. H., Pailler, E., Bosse, T. L., Thaker, M., Almanza, D., Dempster, J. M., Pan, J., Piccioni, F., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.090 · Cited by 90 · see citing works
MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects
Urner-Bloch, U., Urner, M., Jaberg-Bentele, N., Frauchiger, A. L., Dummer, R., & Goldinger, S. M. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.06.018 · Cited by 82 · see citing works
MEK inhibition in non-small cell lung cancer
Stinchcombe, T. E., & Johnson, G. L. (2014) · Lung Cancer · doi:10.1016/j.lungcan.2014.09.005 · Cited by 69 · see citing works
Zimmer, L., Barlesi, F., Martinez-Garcia, M., Dieras, V., Schellens, J. H. M., Spano, J.-P., Middleton, M. R., Calvo, E., Paz-Ares, L., Larkin, J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0341 · Cited by 71 · see citing works
Santarpia, M., Ciappina, G., Spagnolo, C. C., Squeri, A., Passalacqua, M. I., Aguilar, A., Gonzalez-Cao, M., Giovannetti, E., Silvestris, N., & Rosell, R. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-639 · Cited by 65 · 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
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
van Geel, R. M. J. M., van Brummelen, E. M. J., Eskens, F. A. L. M., Huijberts, S. C. F. A., de Vos, F. Y. F. L., Lolkema, M. P. J. K., Devriese, L. A., Opdam, F. L., Marchetti, S., Steeghs, N., et al. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0776-z · Cited by 55 · see citing works
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
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
Current status of MEK inhibitors in the treatment of plexiform neurofibromas
Gross, A. M., Dombi, E., & Widemann, B. C. (2020) · Child's Nervous System · doi:10.1007/s00381-020-04731-2 · Cited by 47 · see citing works
Hu, J., Wei, J., Yim, H., Wang, L., Xie, L., Jin, M. S., Kabir, M., Qin, L., Chen, X., Liu, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01609 · Cited by 43 · see citing works
Šuštić, T., van Wageningen, S., Bosdriesz, E., Reid, R. J. D., Dittmar, J., Lieftink, C., Beijersbergen, R. L., Wessels, L. F. A., Rothstein, R., & Bernards, R. (2018) · Genome Medicine · doi:10.1186/s13073-018-0600-z · Cited by 42 · see citing works
Saturno, G., Lopes, F., Niculescu-Duvaz, I., Niculescu-Duvaz, D., Zambon, A., Davies, L., Johnson, L., Preece, N., Lee, R., Viros, A., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2020.10.483 · Cited by 21 · see citing works
Giopanou, I., & Pintzas, A. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.102859 · Cited by 17 · see citing works
- Authors
- Jänne, P. A., Shaw, A. T., Pereira, J. R., Jeannin, G., Vansteenkiste, J., Barrios, C., Franke, F. A., Grinsted, L., Zazulina, V., Smith, P., Smith, I., & Crinò, L.
- Affiliations
- Massachusetts General Hospital (US)
- Universitair Ziekenhuis Leuven (BE)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- AstraZeneca (United Kingdom) (GB)
- Azienda Ospedaliera di Perugia (IT)
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 14
- Issue
- 1
- Pages
- 38-47
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2114784462
- Cited by
- 655
- References
- 34
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 19 · 2023: 17 · 2022: 19 · 2021: 28 · 2020: 33 · 2019: 40 · 2018: 47 · 2017: 68 · 2016: 81 · 2015: 120 · 2014: 99 · 2013: 57 · 2012: 4
- FWCI
- 72.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- selumetinib, docetaxel, KRAS mutation, non-small cell lung cancer, MEK inhibitors, combination therapy, previously treated patients, overall survival, targeted therapy, advanced non-small cell lung cancer, RAS/RAF pathway, neutropenia, hyperphosphatemia, hyperkalemia
- MeSH terms
- Docetaxel, Adult, Aged, Benzimidazoles, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Prospective Studies, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Disease-Free Survival, ras Proteins, Taxoids, Protein Kinase Inhibitors, Drug-Related Side Effects and Adverse Reactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
