Treating Patients With EGFR-Sensitizing Mutations: First Line or Second Line—Is There a Difference?
Abstract
First-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is a standard treatment for patients with activating EGFR mutations. Six randomized studies have demonstrated consistent improvement in tumor response rate and progression-free survival over platinum-based combination chemotherapy. The only reason to consider EGFR TKI as second-line therapy is that none of the six comparative studies has shown improvement in overall survival, which can be explained by the high proportion of patients from the chemotherapy arm crossing over to the EGFR TKI arm on progression. It is true that patients with EGFR mutations may benefit from second-line EGFR TKI therapy, but we cannot conclude that the benefit is either equal to or inferior to first-line EGFR TKI therapy. To date, there are no direct comparative data between first- and second-line EGFR TKI in patients with activating EGFR mutations. Tumor response rates to second-line EGFR TKI have been inconsistent, which could potentially be explained by the impact of first-line chemotherapy on the abundance of tumor cells with activating EGFR mutations. However, numerous arguments, including assurance on drug exposure, improvement in quality of life, better tolerance by patients with poor performance status, and deferral of whole-brain radiation therapy for patients with brain metastasis, support the general application of first-line EGFR TKI.
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The lack of overall survival difference is most likely due to confounding from crossover treatment.
“As seen in randomized phase 3 studies of first-line EGFR tyrosine kinase inhibitors versus chemotherapy in EGFRmutation-positive NSCLC, this finding is most likely attributable to the confounding effects of crossover treatment.32”
From First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer (2014) · cites this paper as [32]
Cites
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-citationInoue, A., Kobayashi, K., Usui, K., Maemondo, M., Okinaga, S., Mikami, I., Ando, M., Yamazaki, K., Saijo, Y., Gemma, A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.7658 · Cited by 505 · see citing works
Kudoh, S., Takeda, K., Nakagawa, K., Takada, M., Katakami, N., Matsui, K., Shinkai, T., Sawa, T., Goto, I., Semba, H., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.1044 · Cited by 360 · cited 1× · see citing works
“generation cytotoxic agents also reported relatively low tumor response rates and short survival in the elderly population.(36,37)”
BackgroundSutani, A., Nagai, Y., Udagawa, K., Uchida, Y., Koyama, N., Murayama, Y., Tanaka, T., Miyazawa, H., Nagata, M., Kanazawa, M., et al. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603466 · Cited by 167 · see citing works
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First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer
Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408440 · Cited by 3,190 · see citing works
Self-citationYang, J. C.-H., Wu, Y.-L., Schuler, M., Sebastian, M., Popat, S., Yamamoto, N., Zhou, C., Hu, C.-P., O'Byrne, K., Feng, J., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(14)71173-8 · Cited by 1,574 · see citing works
Self-citationProperties of FDA-approved small molecule protein kinase inhibitors
Roskoski, R. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.006 · Cited by 554 · 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
Self-citationLeduc, C., Merlio, J. P., Besse, B., Blons, H., Debieuvre, D., Bringuier, P. P., Monnet, I., Rouquette, I., Fraboulet-Moreau, S., Lemoine, A., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx404 · Cited by 96 · see citing works
Heigener, D. F., Schumann, C., Sebastian, M., Sadjadian, P., Stehle, I., Märten, A., Lüers, A., Griesinger, F., Scheffler, M., & for the Afatinib Compassionate Use Consortium (ACUC) (2015) · The Oncologist · doi:10.1634/theoncologist.2015-0073 · Cited by 78 · see citing works
- Authors
- Mok, T., Yang, J.-J., & Lam, K.-C.
- Affiliations
- Chinese University of Hong Kong (HK)
- Venue
- Journal of Clinical Oncology
- Published
- 2013-03-10
- Volume
- 31
- Issue
- 8
- Pages
- 1081-1088
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2100093357
- Cited by
- 103
- References
- 4
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 15 · 2016: 13 · 2015: 14 · 2014: 18 · 2013: 11 · 2012: 1
- FWCI
- 2.90
- 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 › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- EGFR mutation, EGFR tyrosine kinase inhibitors, first-line therapy, second-line therapy, non-small cell lung cancer, platinum-based chemotherapy, progression-free survival, overall survival, brain metastases, quality of life
- MeSH terms
- Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Prognosis, Survival Analysis, Treatment Outcome, Disease Progression, Protein Kinase Inhibitors, ErbB Receptors
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