Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer and EGFR-Activating Mutations
Abstract
Purpose: ARCHER 1050, a randomized, open-label, phase III study of dacomitinib versus gefitinib in treatment-naïve patients with advanced non–small-cell lung cancer (NSCLC) and activating mutations in EGFR, reported significant improvement in progression-free survival with dacomitinib. The mature overall survival (OS) analysis for the intention-to-treat population is presented here. Patients and Methods: In this multinational, multicenter study, patients age 18 years or older (≥ 20 years in Japan and Korea) who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and newly diagnosed NSCLC with activating mutations in EGFR (exon 19 deletion or exon 21 L858R) were enrolled and randomly assigned in a 1:1 manner to dacomitinib (n = 227) or gefitinib (n = 225). Random assignment was stratified by race (Japanese, Chinese, other East Asian, or non-Asian) and EGFR mutation type. The final OS analysis was conducted with a data cutoff date of February 17, 2017; at that time 220 deaths (48.7%) were observed. Results: During a median follow-up time of 31.3 months, 103 (45.4%) and 117 (52.0%) deaths occurred in the dacomitinib and gefitinib arms, respectively. The estimated hazard ratio for OS was 0.760 (95% CI, 0.582 to 0.993; two-sided P = .044). The median OS was 34.1 months with dacomitinib versus 26.8 months with gefitinib. The OS probabilities at 30 months were 56.2% and 46.3% with dacomitinib and gefitinib, respectively. Preliminary subgroup analyses for OS that are based on baseline characteristics were consistent with the primary OS analysis. Conclusion: In patients with advanced NSCLC and EGFR activating mutations, dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (TKI) to show significant improvement in OS in a phase III randomized study compared with a standard-of-care TKI. Dacomitinib should be considered one of the standard treatment options for these patients.
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In head-to-head trials, afatinib did not show a statistically significant OS difference versus gefitinib.
“there was no statistically significant difference with afatinib versus gefitinib”
From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [44]
Exploratory analysis demonstrated prolonged OS with dacomitinib versus gefitinib.
“exploratory analysis demonstrated prolonged OS with dacomitinib versus gefitinib.”
From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [44]
As a first-line agent in EGFR mutation-sensitive NSCLC, dacomitinib has been demonstrated by many clinical trials to extend overall survival and show significant advantages over first-generation EGFR TKIs.
“As a first-line agent in EGFR mutation-sensitive NSCLC, dacomitinib has been demonstrated by many clinical trials to extend overall survival and show significant advantages over first-generation EGFR TKIs.127,130”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [127]
Dacomitinib is an irreversible second-generation EGFR TKI originally developed by Pfizer and co-developed by SFJ Pharmaceuticals in 2012, and was approved by the FDA in 2018 for metastatic NSCLC with exon 19 deletion and exon 21 replacement.
“Dacomitinib (VizimproTM, PF-299804) (46), also an irreversible second-generation EGFR TKI originally developed by Pfizer and co-developed by SFJ Pharmaceuticals in 2012, was approved by the FDA in 2018 for the treatment of metastatic NSCLC with exon 19 deletion and exon 21 replacement.125–128”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [127]
Duration of response, progression-free survival, and overall survival are even more variable across these trials.
“Even more variable are duration of response to targeted therapy, progression-free survival and overall survival16–26, 28–32, 35.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [22]
In first-line targeted therapy trials for oncogene-addicted NSCLC, objective response rates typically range from 50% to 83%, complete responses are rare, and some patients show de novo resistance.
“Across clinical trials of first-line targeted therapy for oncogene-addicted subgroups of NSCLC, rates of objective response [G] typically range between 50% and 83% and complete responses [G] are rare; in addition, some patients exhibit de novo resistance16–26, 28–32, 35.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [22]
Most second-generation TKIs are dosed at the maximum tolerated doses, resulting in plasma concentrations 10-100 fold greater than concentrations necessary for inhibiting PACC mutations.
“Clinically, second-generation TKIs have been associated with inhibition of wild-type EGFR and related adverse events15,35,36; however, most second-generation TKIs are dosed at the maximum tolerated doses, resulting in plasma concentrations 10–100 fold greater than concentrations necessary for inhibiting PACC mutations.”
From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [35]
Exon 18 mutations are associated with male sex and smoking history.
“an association with the male sex [18] and smoking history has been reported [19,31]”
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-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-citationPark, K., Tan, E.-H., O'Byrne, K., Zhang, L., Boyer, M., Mok, T., Hirsh, V., Yang, J. C.-H., Lee, K. H., Lu, S., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30033-x · Cited by 1,183 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Overall Survival with Osimertinib in Untreated, <i>EGFR</i> -Mutated Advanced NSCLC
Ramalingam, S. S., Vansteenkiste, J., Planchard, D., Cho, B. C., Gray, J. E., Ohe, Y., Zhou, C., Reungwetwattana, T., Cheng, Y., Chewaskulyong, B., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1913662 · Cited by 2,914 · see citing works
Self-citationCo-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
Properties 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
Structure-based classification predicts drug response in EGFR-mutant NSCLC
Robichaux, J. P., Le, X., Vijayan, R. S. K., Hicks, J. K., Heeke, S., Elamin, Y. Y., Lin, H. Y., Udagawa, H., Skoulidis, F., Tran, H., et al. (2021) · Nature · doi:10.1038/s41586-021-03898-1 · Cited by 490 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Robichaux, J. P., Elamin, Y. Y., Vijayan, R. S. K., Nilsson, M. B., Hu, L., He, J., Zhang, F., Pisegna, M., Poteete, A., Sun, H., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.001 · Cited by 242 · see citing works
Nagasaka, M., Zhu, V. W., Lim, S. M., Greco, M., Wu, F., & Ou, S.-H. I. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.11.028 · Cited by 219 · see citing works
Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings
Harvey, R. D., Adams, V. R., Beardslee, T., & Medina, P. (2020) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155220931926 · Cited by 115 · 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
Hochmair, M. J., Morabito, A., Hao, D., Yang, C.-T., Soo, R. A., Yang, J. C.-H., Gucalp, R., Halmos, B., Wang, L., Märten, A., et al. (2019) · Future Oncology · doi:10.2217/fon-2019-0346 · Cited by 85 · see citing works
Cheng, Y. Y., Rath, E. M., Linton, A., Yuen, M. L., Takahashi, K., & Lee, K. (2020) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s186843 · Cited by 31 · see citing works
Self-citation
- Authors
- Mok, T. S., Cheng, Y., Zhou, X., Lee, K. H., Nakagawa, K., Niho, S., Lee, M., Linke, R., Rosell, R., Corral, J., Migliorino, M. R., Pluzanski, A., Sbar, E. I., Wang, T., White, J. L., & Wu, Y.-L.
- Affiliations
- Army Medical University (CN)
- Tony S. Mok, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong; Ying Cheng, Jilin Provincial Cancer Hospital, Changchun; Xiangdong Zhou, First Affiliated Hospital of Third Military Medical University, Chongqing; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Ki Hyeong Lee, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea; Kazuhiko...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-08-01
- Volume
- 36
- Issue
- 22
- Pages
- 2244-2250
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2806325305
- Semantic Scholar
- b34fd43b2dfe61c50329ab9ac4637f95b6546206
- Cited by
- 439
- References
- 3
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 34 · 2023: 38 · 2022: 68 · 2021: 76 · 2020: 78 · 2019: 83 · 2018: 28
- FWCI
- 49.92
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-10-15)
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer
- American Society of Clinical Oncology
- University of Hong Kong
- 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
- dacomitinib, gefitinib, advanced non-small cell lung cancer, EGFR activating mutations, EGFR exon 19 deletion, L858R mutation, EGFR tyrosine kinase inhibitors, second-generation TKIs, overall survival, progression-free survival, treatment-naive patients, subgroup analysis, East Asian patients, Japanese patients
- MeSH terms
- Gefitinib, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Survival Rate, Proportional Hazards Models, Protein Kinase Inhibitors, Quinazolinones, ErbB Receptors
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