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Cited by 1,216Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial

Wu, Yi-Long, Cheng, Ying, Zhou, Xiangdong, Lee, Ki Hyeong, Nakagawa, Kazuhiko, Niho, Seiji, Tsuji, Fumito, Linke, Rolf +10 more·2017·The Lancet Oncology
DOI 10.1016/s1470-2045(17)30608-3
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Abstract

Background Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC).Methods In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients.Findings Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3-23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1-16·6) in the dacomitinib group and 9·2 months (9·1-11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47-0·74; p<0·0001). The most common grade 3-4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia).Interpretation Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population.Funding SFJ Pharmaceuticals Group and Pfizer.

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Crossref · 10.1016/s1470-2045(17)30608-3

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  • In head-to-head trials, both afatinib and dacomitinib have shown significantly improved PFS versus gefitinib.

    “both afatinib and dacomitinib have shown significantly improved PFS versus gefitinib.”

    From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [41]

  • Patients with brain metastases have been excluded from clinical trials, limiting generalizability of trial outcomes to clinical practice.

    “However, patients with brain metastases have been excluded from clinical trials.41 This is of particular significance as it limits the ability to generalize the outcomes of such clinical trials to patients in the clinic.”

    From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [41]

  • The second- and third-generation TKIs have shown significantly longer PFS compared with first-generation TKIs, and osimertinib has shown superior OS compared with first-generation TKIs.

    “The second- and third-generation TKIs have shown significantly longer PFS compared with first-generation TKIs, and the third-generation TKI, osimertinib, has shown superior OS compared with first-generation TKIs.”

    From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [41]

  • Dacomitinib was found to be more promising for progression-free survival compared to gefitinib in a randomized, phase III clinical trial (ARCHER 1050); however, more severe adverse reactions were observed.

    “In addition, dacomitinib was found to be more promising for progression-free survival compared to gefitinib in a randomized, phase III clinical trial (ARCHER 1050); however, more severe adverse reactions were observed.130”

    From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [130]

  • 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 [130]

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Authors
Wu, Y.-L., Cheng, Y., Zhou, X., Lee, K. H., Nakagawa, K., Niho, S., Tsuji, F., Linke, R., Rosell, R., Corral, J., Migliorino, M. R., Pluzanski, A., Sbar, E. I., Wang, T., White, J. L., Nadanaciva, S., Sandin, R., & Mok, T. S.
Affiliations
  • Guangdong General Hospital (CN)
  • Jilin Province Tumor Hospital (CN)
  • Army Medical University (CN)
  • Chungbuk National University (KR)
  • Kindai University Hospital (JP)
  • National Cancer Center Hospital East (JP)
  • Institut Català d'Oncologia (ES)
  • Hospital Universitario Virgen del Rocío (ES)
  • Azienda Ospedaliera San Camillo-Forlanini (IT)
  • Pfizer (United States) (US)
  • Pfizer (Sweden) (SE)
  • Chinese University of Hong Kong (HK)
Corresponding author
Wu, Yi-Long
ORCID
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2017-11
Volume
18
Issue
11
Pages
1454-1466
ISSN
1470-2045 (ISSN-L)
DOI
10.1016/s1470-2045(17)30608-3
OpenAlex
W2760639821
Cited by
1,216
References
9
Citations by year
2026: 65 · 2025: 118 · 2024: 127 · 2023: 150 · 2022: 186 · 2021: 173 · 2020: 155 · 2019: 134 · 2018: 96 · 2017: 10
FWCI
89.56
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Lancet Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
BioClinica
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, EGFR-mutant non-small cell lung cancer, first-line therapy, EGFR tyrosine kinase inhibitors, exon 19 deletion, progression-free survival, treatment safety, adverse events, EGFR mutation status, treatment discontinuation
MeSH terms
Gefitinib, Adult, Aged, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Prognosis, Quinazolines, Confidence Intervals, Survival Analysis, Treatment Outcome, Disease-Free Survival, Genes, erbB-1, Maximum Tolerated Dose, Quinazolinones, Kaplan-Meier Estimate

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