Chemotherapy With Erlotinib or Chemotherapy Alone in Advanced Non-Small Cell Lung Cancer With Acquired Resistance to EGFR Tyrosine Kinase Inhibitors
Open accessAbstract
Purpose.: Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods.: We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results.: Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05–0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48–1.29; p = .34). There was no difference in overall survival. Conclusion.: This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further.
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Prior data on cytotoxic chemotherapy for acquired resistance to EGFR inhibitors indicate short-lived benefit, with median progression-free survival of 4.0 to 5.5 months.
“Existing data for cytotoxic chemotherapy in patients with acquired resistance to EGFR inhibitors suggest that benefits are also of relatively short duration, with studies showing a median progression-free survival of 4.0 to 5.5 months.17,18”
From Rociletinib in <i>EGFR</i>-Mutated Non–Small-Cell Lung Cancer (2015) · cites this paper as [17]
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Cites
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P. (1982) · American Journal of Clinical Oncology · doi:10.1097/00000421-198212000-00014 · Cited by 11,607 · 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
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909530 · Cited by 5,525 · 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
Mitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70364-x · Cited by 4,090 · see citing works
Goldstraw, P., Crowley, J., Chansky, K., Giroux, D. J., Groome, P. A., Rami-Porta, R., Postmus, P. E., Rusch, V., & Sobin, L. (2007) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31812f3c1a · Cited by 3,655 · see citing works
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499 · see citing works
Self-citationGiaccone, G., Herbst, R. S., Manegold, C., Scagliotti, G. V., Rosell, R., Miller, V. A., Natale, R. B., Schiller, J. H., von Pawel, J., Pluzanska, A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.001 · Cited by 1,712 · see citing works
Herbst, R. S., Giaccone, G., Schiller, J. H., Natale, R. B., Miller, V. A., Manegold, C., Scagliotti, G. V., Rosell, R., Oliff, I. A., Reeves, J. A., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.07.215 · Cited by 1,703 · see citing works
Herbst, R. S., Prager, D., Hermann, R., Fehrenbacher, L., Johnson, B. E., Sandler, A., Kris, M. G., Tran, H. T., Klein, P., Li, X., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.840 · Cited by 1,490 · see citing works
Gatzemeier, U., Pluzanska, A., Szczęsna, A., Kaukel, E., Roubec, J., Rosa, F. D., Milanowski, J., Karnicka-Mlodkowski, H., Pešek, M., Serwatowski, P., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.1474 · Cited by 875 · see citing works
Jackman, D., Pao, W., Riely, G. J., Engelman, J. A., Kris, M. G., Jänne, P. A., Lynch, T., Johnson, B. E., & Miller, V. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.7049 · Cited by 793 · see citing works
Self-citationvon Minckwitz, G., du Bois, A., Schmidt, M., Maass, N., Čufer, T., de Jongh, F. E., Maartense, E., Zielinski, C. C., Kaufmann, M., Bauer, W., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.6618 · Cited by 674 · see citing works
Oxnard, G. R., Arcila, M. E., Sima, C. S., Riely, G. J., Chmielecki, J., Kris, M. G., Pao, W., Ladanyi, M., & Miller, V. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2692 · Cited by 627 · see citing works
Self-citationArcila, M. E., Oxnard, G. R., Nafa, K., Riely, G. J., Solomon, S. B., Zakowski, M. F., Kris, M. G., Pao, W., Miller, V. A., & Ladanyi, M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2277 · Cited by 574 · see citing works
Self-citationOptimization of Dosing for EGFR-Mutant Non–Small Cell Lung Cancer with Evolutionary Cancer Modeling
Chmielecki, J., Foo, J., Oxnard, G. R., Hutchinson, K. E., Ohashi, K., Somwar, R., Wang, L., Amato, K. R., Arcila, M. E., Sos, M. L., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002356 · Cited by 520 · see citing works
Self-citationNon–Small Cell Lung Cancer, Version 2.2013
Ettinger, D. S., Akerley, W., Borghaei, H., Chang, A. C., Cheney, R. T., Chirieac, L. R., D’Amico, T. A., Demmy, T. L., Govindan, R., Grannis, F. W., et al. (2013) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2013.0084 · Cited by 443 · see citing works
Self-citationChaft, J. E., Oxnard, G. R., Sima, C. S., Kris, M. G., Miller, V. A., & Riely, G. J. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1468 · Cited by 418 · see citing works
Self-citationDias-Santagata, D. C., Akhavanfard, S., David, S. S., Vernovsky, K., Kuhlmann, G., Boisvert, S. L., Stubbs, H., McDermott, U., Settleman, J. E., Kwak, E. L., et al. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000070 · Cited by 392 · see citing works
Self-citationOxnard, G. R., Arcila, M. E., Chmielecki, J., Ladanyi, M., Miller, V. A., & Pao, W. J. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2571 · Cited by 355 · see citing works
Self-citationWu, Y.-L. L. C., Lee, J. S., Thongprasert, S., Yu, C., Zhang, L., Ladrera, G., Srimuninnimit, V., Sriuranpong, V., Sandoval-Tan, J., Zhu, Y., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70254-7 · Cited by 298 · see citing works
Riely, G. J., Kris, M. G., Zhao, B., Akhurst, T. J., Milton, D. T., Moore, E., Tyson, L. B., Pao, W. J., Rizvi, N. A., Schwartz, L. H., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0560 · Cited by 288 · see citing works
Janne, P. A., Wang, X., Socinski, M. A., Crawford, J., Stinchcombe, T. E., Gu, L., Capelletti, M., Edelman, M. J., Villalona-Calero, M. A., Kratzke, R. A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.1315 · Cited by 241 · see citing works
Where next for gefitinib in patients with lung cancer?
Blackhall, F. H., Ranson, M., & Thatcher, N. (2006) · The Lancet Oncology · doi:10.1016/s1470-2045(06)70725-2 · Cited by 123 · see citing works
Extra, J.-M., Antoine, É.-C., Vincent‐Salomon, A., et al. (2010) · The Oncologist · doi:10.1634/theoncologist.2009-0029 · Cited by 110 · see citing works
Epidermal Growth Factor ReceptorMutation Testing in the Care of Lung Cancer Patients
Sequist, L. V. D., Joshi, V. A., Janne, P. A., Bell, D. W., Fidias, P. M., Lindeman, N. I., Louis, D. N., Lee, J. C., Mark, E. J., Longtine, J., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0099 · Cited by 81 · see citing works
Self-citationHirsch, F. R., Kabbinavar, F. F., Eisen, T. G., Martins, R. G., Schnell, F. M., Dziadziuszko, R., Richardson, K., Richardson, F. C., Wacker, B., Sternberg, D., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.4929 · Cited by 79 · see citing works
Oxnard, G. R., Janjigian, Y. Y., Arcila, M. E., Sima, C. S., Kass, S. L., Riely, G. J., Pao, W. J., Kris, M. G., Ladanyi, M., Azzoli, C. G., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1080 · Cited by 61 · see citing works
Self-citationSecond‐line treatments after first‐line gefitinib therapy in advanced nonsmall cell lung cancer
Wu, J., Shih, J., Yang, C., Chen, K., Ho, C., Yu, C., & Yang, P. (2009) · International Journal of Cancer · doi:10.1002/ijc.24657 · Cited by 58 · see citing works
Riely, G. J., Rizvi, N. A., Kris, M. G., Milton, D. T., Solit, D. B., Rosen, N. X., Senturk, E., Azzoli, C. G., Brahmer, J. R., Sirotnak, F. M., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.4656 · Cited by 56 · see citing works
Yoshimura, N., Okishio, K., Mitsuoka, S., et al. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182762bfb · Cited by 49 · see citing works
Aerts, J. G. J. V., Codrington, H., Lankheet, N. A. G., Burgers, S. A., Biesma, B., Dingemans, A. C., Vincent, A. D., Dalesio, O., Groen, H. J. M., & Smit, E. F. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt341 · Cited by 44 · see citing works
Halmos, B., Pennell, N. A., Otterson, G. A., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.8114 · Cited by 6 · see citing works
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Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454 · see citing works
Weickhardt, A. J., Scheier, B., Burke, J. M., Gan, G., Lu, X., Bunn, P. A., Aisner, D. L., Gaspar, L. E., Kavanagh, B. D., Doebele, R. C., et al. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182745948 · Cited by 684 · see citing works
Rociletinib in <i>EGFR</i>-Mutated Non–Small-Cell Lung Cancer
Sequist, L. V., Soria, J.-C., Goldman, J. W., Wakelee, H. A., Gadgeel, S. M., Varga, A., Papadimitrakopoulou, V., Solomon, B. J., Oxnard, G. R., Dziadziuszko, R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1413654 · Cited by 665 · see citing works
Self-citationMarcoux, N., Gettinger, S. N., O’Kane, G., Arbour, K. C., Neal, J. W., Husain, H., Evans, T. L., Brahmer, J. R., Muzikansky, A., Bonomi, P. D., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.01585 · Cited by 500 · see citing works
Self-citationEpidermal Growth Factor Receptor Tyrosine Kinase Inhibitor–Resistant Disease
Ohashi, K., Maruvka, Y. E., Michor, F., & Pao, W. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3912 · Cited by 467 · see citing works
Soria, J.-C., Wu, Y.-L., Nakagawa, K., Kim, S.-W., Yang, J.-J., Ahn, M.-J., Wang, J., Yang, J. C.-H., Lu, Y., Atagi, S., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00121-7 · Cited by 413 · see citing works
Reguart, N., & Remon, J. (2015) · Future Oncology · doi:10.2217/fon.15.15 · Cited by 91 · see citing works
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Yap, T. A., Macklin-Doherty, A., & Popat, S. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2016.10.014 · Cited by 38 · see citing works
- Authors
- Goldberg, S. B., Oxnard, G. R., Digumarthy, S., Muzikansky, A., Jackman, D. M., Lennes, I. T., & Sequist, L. V.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Goldberg, Sarah B.
- ORCID
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-26
- Volume
- 18
- Issue
- 11
- Pages
- 1214-1220
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- PMC
- PMC3825307
- OpenAlex
- W2150371178
- Cited by
- 130
- References
- 34
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 10 · 2018: 7 · 2017: 16 · 2016: 11 · 2015: 24 · 2014: 27 · 2013: 6 · 2012: 2
- FWCI
- 18.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Oncologist (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conquer Cancer Foundation of the American Society of Clinical Oncology
- National Cancer Institute (P50-CA090578)
- 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 › HER2/EGFR in Cancer Research
- Keywords
- erlotinib, EGFR tyrosine kinase inhibitors, acquired drug resistance, EGFR-mutant non-small cell lung cancer, combination chemotherapy, objective response rate, progression-free survival, overall survival
- MeSH terms
- Pemetrexed, Erlotinib Hydrochloride, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Organoplatinum Compounds, Quinazolines, Retrospective Studies, Disease-Free Survival, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors
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