Effectiveness of Gefitinib against Non–Small-Cell Lung Cancer with the Uncommon EGFR Mutations G719X and L861Q
Open accessAbstract
INTRODUCTION: In non-small-cell lung cancer, an exon 19 deletion and an L858R point mutation in the epidermal growth factor receptor (EGFR) are predictors of a response to EGFR-tyrosine kinase inhibitors. However, it is uncertain whether other uncommon EGFR mutations are associated with sensitivity to EGFR-tyrosine kinase inhibitors. METHODS: A post-hoc analysis to assess prognostic factors was performed with the use of patients with EGFR mutations (exon 19 deletion, L858R, G719X, and L861Q) who were treated with gefitinib in the NEJ002 study, which compared gefitinib with carboplatin-paclitaxel as the first-line therapy. RESULTS: In the NEJ002 study, 225 patients with EGFR mutations received gefitinib at any treatment line. The Cox proportional hazards model indicated that performance status, response to chemotherapy, response to gefitinib, and mutation types were significant prognostic factors. Overall survival (OS) was significantly shorter among patients with uncommon EGFR mutations (G719X or L861Q) compared with OS of those with common EGFR mutations (12 versus 28.4 months; p = 0.002). In the gefitinib group (n = 114), patients with uncommon EGFR mutations had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001). By contrast, OS was similar between patients with uncommon mutations and those with common mutations in the carboplatin-paclitaxel group (n = 111; 22.8 versus 28 months; p = 0.358). CONCLUSIONS: The post-hoc analyses clearly demonstrated shorter survival for gefitinib-treated patients with uncommon EGFR mutations compared with the survival of those with common mutations and suggest that the first-line chemotherapy may be relatively effective for non-small-cell lung cancer with uncommon EGFR mutations.
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Patients with G719X mutations treated with first-generation EGFR TKIs have lower overall response rates (14-53%).
“lower overall response rate (ORR) (14–53%) in patients harboring G719X mutations, treated with first-generation EGFR TKIs [12,21,35,36]”
The G719X + S768I compound mutation (about 1% of all EGFR mutations) is sensitive to first-generation EGFR TKIs but to a lesser extent than classic mutations, with ORR approximately 50% and median PFS of 8-10 months.
“One of the most frequent compound mutations is the G719X + S768I (about 1% of all EGFR mutations) [37,84], which has been shown to be sensitive to the first-generation EGFR TKIs, but to a lesser extent than classic mutations (ORR approximately 50% and median PFS of 8–10 months) [12,33,46].”
In NEJ002, OS was lower for rare mutations (G719X or L861Q) than common (p=0.002); gefitinib-treated rare had shorter OS (11.9 vs 29.3 months, p<0.001); carboplatin-paclitaxel had similar OS (p=0.358).
“In the NEJ002 study, OS was significantly lower for patients with rare mutations (G719X or L861Q) than for those with common EGFR mutations (p ¼ 0.002).Patients with rare EGFR mutations (G719X or L861Q) treated with gefitinib had a significantly shorter OS (11.9 versus 29.3 months; p < 0.001).Interestingly, OS was similar between patients with uncommon and common mutations when treated with carbop”
From Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Whose Tumors Harbor Uncommon EGFR Mutations (2016) · cites this paper as [35]
Several retrospective studies and case reports of first-generation EGFR-TKIs showed inconsistent responses in patients with NSCLC harboring uncommon EGFR mutations.
“Several retrospective studies and case reports of fi rst-generation EGFR-TKIs showed inconsistent responses in patients with NSCLC harboring uncommon EGFR mutations.”
From Osimertinib for Patients With Non–Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09) (2020) · cites this paper as [24]
In the NEJ002 trial, the response rate and PFS with gefitinib were significantly lower in patients with uncommon EGFR mutations (G719X or L861Q) compared with those with common EGFR mutations (20% v 76%; 2.2 months v 11.4 months).
“In the NEJ002 trial, the response rate and PFS with ge fi tinib were signi fi cantly lower in patients with uncommon EGFR mutations (G719X or L861Q) compared with those with common EGFR mutations (20% v 76%; 2.2 months v 11.4 months). 24”
From Osimertinib for Patients With Non–Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09) (2020) · cites this paper as [24]
Several studies have shown that 1G EGFR-TKI are less effective in patients with NSCLC harboring uncommon EGFR mutations compared with patients harboring common EGFR mutations.
“Several studies, although very small, have shown that 1G EGFR‐TKI are less effective in patients with NSCLC harboring such uncommon EGFR mutations, compared with patients harboring common EGFR mutations.”
Most studies of uncommon EGFR mutations are retrospective case reports and show differential sensitivity by mutation type.
“Most of the studies are retrospective, comprising individual case reports in patients treated with both firstand second-generation TKIs that highlight differential sensitivities based on mutation type.62,63”
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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 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
Self-citationRosell, 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
Erlotinib 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
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
Zhou, C., Wu, Y.-L., Chen, G., Feng, J., Liu, X.-Q., Wang, C., Zhang, S., Wang, J., Zhou, S., Ren, S., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70184-x · Cited by 4,081 · see citing works
Detection of Mutations in <i>EGFR</i> in Circulating Lung-Cancer Cells
Maheswaran, S., Sequist, L. V., Nagrath, S., Ulkus, L., Brannigan, B., Collura, C. V., Inserra, E., Diederichs, S., Iafrate, A. J., Bell, D. W., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0800668 · Cited by 1,617 · 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
Yun, C.-H., Boggon, T. J., Li, Y., Woo, M. S., Greulich, H., Meyerson, M., & Eck, M. J. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.12.017 · Cited by 1,192 · cited 1× · see citing works
“In vitro studies have indicated that the affinity of gefitinib for EGFR proteins with uncommon EGFR mutations is lower than the affinity of gefitinib for EGFR proteins with common EGFR mutations.(25) A sixfold or 14-fold higher concentration of gefitinib was required to inhibit the growth of cells expressing G719X or…”
ResultMiller, V. A., Hirsh, V., Cadranel, J., Chen, Y.-M., Park, K., Kim, S.-W., Zhou, C., Su, W.-C., Wang, M., Sun, Y., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70087-6 · Cited by 961 · see citing works
Sequist, L. V., Martins, R. G., Spigel, D., Grunberg, S. M., Spira, A., Jänne, P. A., Joshi, V. A., McCollum, D., Evans, T. L., Muzikansky, A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.8494 · Cited by 820 · 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
Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer
Mitsudomi, T., & Yatabe, Y. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07448.x · Cited by 560 · see citing works
Nagai, Y., Miyazawa, H., Huqun, Tanaka, T., Udagawa, K., Kato, M., Fukuyama, S., Yokote, A., Kobayashi, K., Kanazawa, M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0331 · Cited by 503 · see citing works
Self-citationWu, J.-Y., Yu, C.-J., Chang, Y.-C., Yang, C.-H., Shih, J.-Y., & Yang, P.-C. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3408 · Cited by 463 · see citing works
Sequist, L. V. D., Besse, B., Lynch, T. J., Miller, V. A., Wong, K., Gitlitz, B. J., Eaton, K. D., Zacharchuk, C., Freyman, A., Powell, C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.9414 · Cited by 432 · see citing works
Frequency of and variables associated with the EGFR mutation and its subtypes
Tanaka, T., Matsuoka, M., Sutani, A., Gemma, A., Maemondo, M., Inoue, A., Okinaga, S., Nagashima, M., Oizumi, S., Uematsu, K., et al. (2009) · International Journal of Cancer · doi:10.1002/ijc.24746 · Cited by 183 · see citing works
Self-citationEffects of Erlotinib in <i>EGFR</i> Mutated Non-Small Cell Lung Cancers with Resistance to Gefitinib
Costa, D. B., Nguyen, K.-S. H., Cho, B. C., Sequist, L. V., Jackman, D. M., Riely, G. J., Yeap, B. Y., Halmos, B., Kim, J. H., Jänne, P. A., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1455 · Cited by 171 · see citing works
Kancha, R. K., von Bubnoff, N., Peschel, C., & Duyster, J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1757 · Cited by 168 · see citing works
De Pas, T., Toffalorio, F., Manzotti, M., Fumagalli, C., Spitaleri, G., Catania, C., Delmonte, A., Giovannini, M., Spaggiari, L., de Braud, F., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318227e8c6 · Cited by 138 · see citing works
Pallis, A. G., Voutsina, A., Kalikaki, A., Souglakos, J., Briasoulis, E. C., Murray, S. J., Koutsopoulos, A. V., Tripaki, M., Stathopoulos, E. N., Mavroudis, D., et al. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6604068 · Cited by 90 · see citing works
Rizvi, N. A., Rusch, V. W., Pao, W. J., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2102 · Cited by 70 · see citing works
Masago, K., Fujita, S., Irisa, K., Kim, Y. H., Ichikawa, M., Mio, T., & Mishima, M. (2010) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyq087 · Cited by 51 · see citing works
Kancha, R. K., Peschel, C., & Duyster, J. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182021f3e · Cited by 49 · see citing works
Ackerman, A., Goldstein, M. A., Kobayashi, S. S., et al. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182635ab4 · Cited by 34 · see citing works
Ong, M., Kwan, K. F., Kamel‐Reid, S., & Vincent, M. D. (2012) · Current Oncology · doi:10.3747/co.19.908 · Cited by 18 · see citing works
Sharma, A., Tan, T. H., Cheetham, G., Scott, H. S., & Brown, M. P. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31825134ac · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [23]Therasse P Arbuck SG Eisenhauer EA New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000 92 205 216 10655437
Cited by
Sorted by citations
Yang, J. C.-H., Sequist, L. V., Geater, S. L., Tsai, C.-M., Mok, T. S. K., Schuler, M., Yamamoto, N., Yu, C.-J., Ou, S.-H. I., Zhou, C., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00026-1 · Cited by 1,002 · see citing works
Kobayashi, Y., & Mitsudomi, T. (2016) · Cancer Science · doi:10.1111/cas.12996 · Cited by 413 · see citing works
Cho, J. H., Lim, S. H., An, H. J., Kim, K. H., Park, K. U., Kang, E. J., Choi, Y. H., Ahn, M. S., Lee, M. H., Sun, J.-M., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.00931 · Cited by 358 · see citing works
Chiu, C.-H., Yang, C.-T., Shih, J.-Y., Huang, M.-S., Su, W.-C., Lai, R.-S., Wang, C.-C., Hsiao, S.-H., Lin, Y.-C., Ho, C.-L., et al. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000504 · Cited by 241 · see citing works
Tan, D. S. W., Yom, S. S., Tsao, M. S., Pass, H. I., Kelly, K., Peled, N., Yung, R. C., Wistuba, I. I., Yatabe, Y., Unger, M., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.05.008 · Cited by 201 · see citing works
A comprehensive review of uncommon EGFR mutations in patients with non-small cell lung cancer
Tu, H.-Y., Ke, E.-E., Yang, J.-J., Sun, Y.-L., Yan, H.-H., Zheng, M.-Y., Bai, X.-Y., Wang, Z., Su, J., Chen, Z.-H., et al. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.11.005 · Cited by 182 · see citing works
Russo, A., Franchina, T., Ricciardi, G., Battaglia, A., Picciotto, M., & Adamo, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061431 · Cited by 110 · see citing works
Shen, Y.-C., Tseng, G.-C., Tu, C.-Y., Chen, W.-C., Liao, W.-C., Chen, W.-C., Li, C.-H., Chen, H.-J., & Hsia, T.-C. (2017) · Lung Cancer · doi:10.1016/j.lungcan.2017.06.007 · Cited by 99 · see citing works
Xu, J., Jin, B., Chu, T., Dong, X., Yang, H., Zhang, Y., Wu, D., Lou, Y., Zhang, X., Wang, H., et al. (2016) · Lung Cancer · doi:10.1016/j.lungcan.2016.01.018 · Cited by 92 · 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
Banno, E., Togashi, Y., Nakamura, Y., Chiba, M., Kobayashi, Y., Hayashi, H., Terashima, M., de Velasco, M. A., Sakai, K., Fujita, Y., et al. (2016) · Cancer Science · doi:10.1111/cas.12980 · Cited by 87 · see citing works
Cheng, G., Song, Z., & Chen, D. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s108242 · Cited by 77 · see citing works
Kuiper, J. L., Hashemi, S. M. S., Thunnissen, E., Snijders, P. J. F., Grünberg, K., Bloemena, E., Sie, D., Postmus, P. E., Heideman, D. A. M., & Smit, E. F. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.372 · Cited by 73 · see citing works
Pilotto, S., Rossi, A., Vavalà, T., Follador, A., Tiseo, M., Galetta, D., Morabito, A., Di Maio, M., Martelli, O., Caffo, O., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2017.05.016 · Cited by 46 · see citing works
Frega, S., Lorenzi, M., Fassan, M., Indraccolo, S., Calabrese, F., Favaretto, A., Bonanno, L., Polo, V., Zago, G., Lunardi, F., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15945 · Cited by 17 · see citing works
- Authors
- Watanabe, S., Minegishi, Y., Yoshizawa, H., Maemondo, M., Inoue, A., Sugawara, S., Isobe, H., Harada, M., Ishii, Y., Gemma, A., Hagiwara, K., & Kobayashi, K.
- Affiliations
- Tohoku University (JP)
- Nippon Medical School (JP)
- Niigata University Medical and Dental Hospital (JP)
- Miyagi Prefectural Hospital Organization (JP)
- Sendai Kousei Hospital (JP)
- KKR Sapporo Medical Center (JP)
- Sapporo National Hospital (JP)
- Dokkyo University (JP)
- Saitama Medical University (JP)
- Saitama International Medical Center (JP)
- Corresponding author
- Yoshizawa, Hirohisa
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 9
- Issue
- 2
- Pages
- 189-194
- ISSN
- 1556-0864 (ISSN-L)
- PMC
- PMC4132025
- OpenAlex
- W2053603900
- Cited by
- 204
- References
- 28
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 16 · 2023: 9 · 2022: 21 · 2021: 19 · 2020: 24 · 2019: 29 · 2018: 12 · 2017: 23 · 2016: 19 · 2015: 16 · 2014: 4 · 2013: 2
- FWCI
- 16.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Tokyo Cooperative Oncology Group
- 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 › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- gefitinib, non-small cell lung cancer, EGFR mutation, G719X, L861Q, EGFR tyrosine kinase inhibitors, prognostic factors, overall survival, carboplatin-paclitaxel, first-line chemotherapy, exon 19 deletion, L858R mutation
- MeSH terms
- Gefitinib, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Follow-Up Studies, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Prognosis, Quinazolines, Retrospective Studies, Survival Rate, Polymerase Chain Reaction, Carboplatin, Paclitaxel, Sequence Deletion, ErbB Receptors
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