Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial
Abstract
PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation-positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. CONCLUSION These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.
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Retrospective analyses of large phase III trials reported inferior ORR than commonly observed in the front-line setting in EGFR-mutated patients treated with EGFR TKIs after chemotherapy.
“However, retrospective analyses of large phase III trials reported inferior ORR than commonly observed in the front-line setting in EGFR-mutated patients treated with EGFR TKIs after chemotherapy [41–44].”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [42]
Cites
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · 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
Self-citationErlotinib in Previously Treated Non–Small-Cell Lung Cancer
Shepherd, F. A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E. H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050753 · Cited by 5,419 · see citing works
Self-citationA sharper Bonferroni procedure for multiple tests of significance
HOCHBERG, Y. (1988) · Biometrika · doi:10.1093/biomet/75.4.800 · Cited by 4,829 · see citing works
<i>EGFR</i> Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964 · see citing works
Fukuoka, M., Yano, S., Giaccone, G., Tamura, T., Nakagawa, K., Douillard, J., Nishiwaki, Y., Vansteenkiste, J., Kudoh, S., Rischin, D., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.10.038 · Cited by 2,871 · see citing works
Self-citationKris, M. G., Natale, R. B., Herbst, R. S., Lynch, Jr., Prager, D., Belani, C. P., Schiller, J. H., Kelly, K., Spiridonidis, H., Sandler, A., et al. (2003) · JAMA · doi:10.1001/jama.290.16.2149 · Cited by 2,517 · see citing works
Thatcher, N., Chang, A., Parikh, P., Rodrigues Pereira, J., Ciuleanu, T., von Pawel, J., Thongprasert, S., Tan, E. H., Pemberton, K., Archer, V., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67625-8 · Cited by 2,079 · see citing works
Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome
Tsao, M., Sakurada, A., Cutz, J.-C., Zhu, C., Kamel‐Reid, S., Squire, J. A., Lorimer, I. A. J., Zhang, T., Liu, G., Daneshmand, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050736 · Cited by 1,815 · see citing works
Self-citationVinorelbine 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
Self-citationCappuzzo, F., Hirsch, F. R., Rossi, E., Bartolini, S., Ceresoli, G. L., Bemis, L., Haney, J., Witta, S. E., Danenberg, K. D., Domenichini, I., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji112 · Cited by 1,538 · see citing works
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517 · see citing works
Hirsch, F. R., Varella‐Garcia, M., Bunn, P. A., Maria, M. V. D., Veve, R., Bremnes, R. M., Barón, A. E., Zeng, C., & Franklin, W. A. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.11.069 · Cited by 1,476 · 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
Kim, E. S., Hirsh, V., Mok, T. S. K., Socinski, M. A., Gervais, R., Wu, Y.-L. L. C., Li, L.-Y., Watkins, C. L., Sellers, M. V., Lowe, E., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61758-4 · Cited by 1,241 · see citing works
Self-citationHirsch, F. R., Varella-Garcia, M., Bunn, P. A., Franklin, W. A., Dziadziuszko, R., Thatcher, N., Chang, A., Parikh, P., Pereira, J. R., Ciuleanu, T., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.3958 · Cited by 703 · see citing works
Self-citationZhu, C.-Q., da Cunha Santos, G., Ding, K., Sakurada, A., Cutz, J.-C., Liu, N., Zhang, T., Marrano, P., Whitehead, M., Squire, J. A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.8924 · Cited by 661 · see citing works
Self-citationSequist, L. V. D., Bell, D. W., Lynch, T. J., & Haber, D. A. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.3585 · Cited by 617 · see citing works
Massarelli, E., Varella‐Garcia, M., Tang, X., Xavier, A. C., Ozburn, N. C., Liu, D. D., Bekele, B. N., Herbst, R. S., & Wistuba, I. I. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3043 · Cited by 594 · see citing works
Hirsch, F. R., Varella‐Garcia, M., McCoy, J., West, H., Xavier, A. C., Gumerlock, P. H., Bunn, P. A., Franklin, W. A., Crowley, J. J., & Gandara, D. R. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.2823 · Cited by 570 · see citing works
Cappuzzo, F., Marchetti, A., Skokan, M. C., Rossi, E., Gajapathy, S., Felicioni, L., Grammastro, M. D., Sciarrotta, M., Buttitta, F., Incarbone, M., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.1635 · Cited by 557 · see citing works
Maruyama, R., Nishiwaki, Y., Tamura, T., Yamamoto, N., Tsuboi, M., Nakagawa, K., Shinkai, T., Negoro, S., Imamura, F., Eguchi, K., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.0185 · Cited by 367 · see citing works
Han, S., Kim, T., Jeon, Y. K., Hwang, P. G., Im, S., Lee, K.-H., Kim, J. H., Kim, D., Heo, D. S., Kim, N. K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2845 · Cited by 250 · see citing works
Gow, C., Chang, Y., Hsu, Y.-C., Tsai, M.-F., Wu, C., Yu, C., Yang, J. C., Lee, Y., Yang, P., & Shih, J. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn679 · Cited by 211 · see citing works
Sequist, L. V. D., Joshi, V. A., Janne, P. A., Muzikansky, A., Fidias, P. M., Meyerson, M. M., Haber, D. A., Kucherlapati, R., Johnson, B. E., & Lynch, T. J. (2007) · The Oncologist · doi:10.1634/theoncologist.12-1-90 · Cited by 161 · see citing works
Čufer, T., Vrdoljak, E., Gaafar, R. M., Erensoy, I., & Pemberton, K. (2006) · Anti-Cancer Drugs · doi:10.1097/01.cad.0000203381.99490.ab · Cited by 151 · see citing works
Petersen, S., Aninat-Meyer, M., Schlüns, K., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.1999.0878 · Cited by 145 · see citing works
Italiano, A., Burel‐Vandenbos, F., Otto, J., Mouroux, J., Fontaine, D., Marcy, P. Y., Cardot‐Leccia, N., Thyss, A., & Pédeutour, F. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl038 · Cited by 128 · see citing works
Bozzetti, C., Tiseo, M., Lagrasta, C. A., Nizzoli, R., Guazzi, A., Leonardi, F., Gasparro, D., Spiritelli, E., Rusca, M., Carbognani, P., et al. (2008) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31815e8ba2 · Cited by 62 · see citing works
Dziadziuszko, R., Holm, B., Skov, B. G., et al. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl407 · Cited by 47 · see citing works
Lee, D., Kim, S., Park, K., Kim, J., Lee, J., Shin, S., Kang, J. H., Suh, C., Ahn, M.-J., & Ahn, J.-B. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.8025 · Cited by 27 · see citing works
Toschi, L., Metro, G., Magrini, E., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.24.18_suppl.7111 · Cited by 5 · see citing works
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Lindeman, N. I., Cagle, P. T., Beasley, M. B., Chitale, D. A., Dacic, S., Giaccone, G., Jenkins, R. B., Kwiatkowski, D. J., Saldivar, J.-S., Squire, J., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318290868f · Cited by 1,280 · see citing works
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
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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
Ciuleanu, T., Stelmakh, L., Cicenas, S., Miliauskas, S., Grigorescu, A. C., Hillenbach, C., Johannsdottir, H. K., Klughammer, B., & Gonzalez, E. E. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70385-0 · Cited by 374 · see citing works
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Uprety, D., & Adjei, A. A. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102070 · Cited by 271 · see citing works
Kawaguchi, T., Ando, M., Asami, K., Okano, Y., Fukuda, M., Nakagawa, H., Ibata, H., Kozuki, T., Endo, T., Tamura, A., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.52.4694 · Cited by 260 · 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
Russo, A., Franchina, T., Rita Ricciardi, G. R., Picone, A., Ferraro, G., Zanghì, M., Toscano, G., Giordano, A., & Adamo, V. (2015) · Oncotarget · doi:10.18632/oncotarget.4254 · Cited by 173 · see citing works
He, M., Capelletti, M., Nafa, K., Yun, C.-H., Arcila, M. E., Miller, V. A., Ginsberg, M. S., Zhao, B., Kris, M. G., Eck, M. J., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2361 · Cited by 149 · see citing works
Lee, J.-K., Hahn, S., Kim, D.-W., Suh, K. J., Keam, B., Kim, T. M., Lee, S.-H., & Heo, D. S. (2014) · JAMA · doi:10.1001/jama.2014.3314 · Cited by 141 · see citing works
Karampeazis, A., Voutsina, A., Souglakos, J., Kentepozidis, N., Giassas, S., Christofillakis, C., Kotsakis, A., Papakotoulas, P., Rapti, A., Agelidou, M., et al. (2013) · Cancer · doi:10.1002/cncr.28132 · Cited by 113 · see citing works
Guan, J.-L., Zhong, W.-Z., An, S.-J., Yang, J.-J., Su, J., Chen, Z.-H., Yan, H.-H., Chen, Z.-Y., Huang, Z.-M., Zhang, X.-C., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2754-z · Cited by 87 · see citing works
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- Authors
- Douillard, J.-Y., Shepherd, F. A., Hirsh, V., Mok, T., Socinski, M. A., Gervais, R., Liao, M.-L., Bischoff, H., Reck, M., Sellers, M. V., Watkins, C. L., Speake, G., Armour, A. A., & Kim, E. S.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2010-02-10
- Volume
- 28
- Issue
- 5
- Pages
- 744-752
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2104748005
- Cited by
- 492
- References
- 33
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 17 · 2019: 11 · 2018: 16 · 2017: 27 · 2016: 31 · 2015: 44 · 2014: 58 · 2013: 75 · 2012: 80
- FWCI
- 54.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- 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
- gefitinib, docetaxel, non-small cell lung cancer, EGFR mutation, EGFR copy number, KRAS mutation, predictive biomarkers, progression-free survival, objective response rate, previously treated patients, EGFR tyrosine kinase inhibitors
- MeSH terms
- Docetaxel, Gefitinib, Antineoplastic Agents, Biopsy, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunohistochemistry, Lung Neoplasms, Male, Mutation, Predictive Value of Tests, Prospective Studies, Proto-Oncogene Proteins, Quinazolines, Time Factors, Biomarkers, Tumor, Logistic Models, Proportional Hazards Models, Odds Ratio, Survival Analysis, Proto-Oncogene Proteins p21(ras), Treatment Outcome, In Situ Hybridization, Fluorescence, Risk Assessment, Disease-Free Survival, Patient Selection, Gene Dosage, ras Proteins, Taxoids, Protein Kinase Inhibitors, ErbB Receptors
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