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Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 5, pp 955–963 | Cite as

A randomized phase II trial of erlotinib vs. S-1 as a third- or fourth-line therapy for patients with wild-type EGFR non-small cell lung cancer (HOT1002)

  • Yasuyuki Ikezawa
  • Hajime Asahina
  • Satoshi Oizumi
  • Masahiro Watanabe
  • Kei Takamura
  • Yasutaka Kawai
  • Noriyuki Yamada
  • Toshiyuki Harada
  • Ichiro Kinoshita
  • Yuka Fujita
  • Eisaku Miyauchi
  • Takahiro Ogi
  • Toraji Amano
  • Megumi Furuta
  • Jun Sakakibara-Konishi
  • Hiroshi Nishihara
  • Hirotoshi Dosaka-Akita
  • Hiroshi Isobe
  • Masaharu Nishimura
  • on behalf of Hokkaido Lung Cancer Clinical Study Group
Original Article

Abstract

Purpose

A high proportion of patients with wild-type EGFR non-small cell lung cancer (NSCLC) receive third-line therapy and beyond, with no prospective randomized trials addressing the issue. This study aimed to select the most suitable regimen as a third- or fourth-line therapy for wild-type EGFR NSCLC.

Methods

This multicenter, randomized phase II study in Japan included patients with recurrent or advanced NSCLC with wild-type or unknown EGFR, who progressed after two or three previous chemotherapies. The patients were randomly assigned to erlotinib (150 mg/day, days 1–21) or S-1 (80–120 mg/day, days 1–14) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), toxicity, and quality of life (QOL).

Results

From 2011 to 2016, 37 patients were randomly assigned to receive erlotinib (E arm, n = 19) and S-1 (S arm, n = 18). This study was terminated prematurely because of poor patient accrual. DCR/ORR were 42.1%/15.8% in the E arm and 66.7%/16.7% in the S arm. Median PFS/OS were 1.6 months/8.0 months in the E arm and 3.3 months/12.2 months in the S arm. In both groups, the most commonly reported grade 3–4 toxicities were fatigue, anorexia, and nausea. One grade 5 pneumonitis occurred in the S arm. No significant difference was seen in QOL.

Conclusions

S-1 as a third- or fourth-line therapy for wild-type EGFR NSCLC showed numerically better clinical outcomes than erlotinib.

Clinical trial registration no.

UMIN000005308.

Keywords

Erlotinib S-1 Non-small cell lung cancer Third-line therapy Fourth-line therapy 

Abbreviations

NSCLC

Non-small cell lung cancer

DCR

Disease control rate

OS

Overall survival

PFS

Progression-free survival

ORR

Objective response rate

QOL

Quality of life

HOT

Hokkaido oncology trial

ECOG PS

Eastern cooperative oncology group performance status

Gr

Grade

BSA

Body surface area

FACT-L

Functional assessment of cancer therapy-lung

CR

Complete response

PR

Partial response

SD

Stable disease

CI

Confidence interval

HR

Hazard ratio

Notes

Acknowledgements

We thank the patients and their families as well as all of the investigators.

Compliance with ethical standards

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The all authors declare that they have no conflict of interest.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of all participating institutions (clinical trial registration no. UMIN000005308).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Supplementary material 1 (PPTX 40 KB)
280_2017_3432_MOESM2_ESM.pptx (57 kb)
Supplementary material 2 (PPTX 56 KB)
280_2017_3432_MOESM3_ESM.pptx (57 kb)
Supplementary material 3 (PPTX 56 KB)
280_2017_3432_MOESM4_ESM.docx (26 kb)
Supplementary material 4 (DOCX 25 KB)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Yasuyuki Ikezawa
    • 1
    • 2
  • Hajime Asahina
    • 1
  • Satoshi Oizumi
    • 1
    • 3
  • Masahiro Watanabe
    • 3
  • Kei Takamura
    • 4
  • Yasutaka Kawai
    • 2
  • Noriyuki Yamada
    • 3
    • 5
  • Toshiyuki Harada
    • 6
  • Ichiro Kinoshita
    • 7
  • Yuka Fujita
    • 8
  • Eisaku Miyauchi
    • 9
  • Takahiro Ogi
    • 4
  • Toraji Amano
    • 7
  • Megumi Furuta
    • 1
  • Jun Sakakibara-Konishi
    • 1
  • Hiroshi Nishihara
    • 10
  • Hirotoshi Dosaka-Akita
    • 7
  • Hiroshi Isobe
    • 11
  • Masaharu Nishimura
    • 1
  • on behalf of Hokkaido Lung Cancer Clinical Study Group
  1. 1.First Department of MedicineHokkaido University HospitalSapporoJapan
  2. 2.Department of Respiratory MedicineOji General HospitalTomakomaiJapan
  3. 3.Department of Respiratory MedicineNational Hospital Organization Hokkaido Cancer CenterSapporoJapan
  4. 4.Department of Respiratory MedicineObihiro-Kosei General HospitalObihiroJapan
  5. 5.Department of Respiratory MedicineIwamizawa Municipal General HospitalIwamizawaJapan
  6. 6.Center for Respiratory DiseasesJCHO Hokkaido HospitalSapporoJapan
  7. 7.Department of Medical Oncology, Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporoJapan
  8. 8.Department of Respiratory MedicineNational Hospital Organization Asahikawa Medical CenterAsahikawaJapan
  9. 9.Department of Respiratory MedicineTohoku University School of MedicineSendaiJapan
  10. 10.Department of Translational PathologyHokkaido University Graduate School of MedicineSapporoJapan
  11. 11.Department of Respiratory MedicineKKR Sapporo Medical CenterSapporoJapan

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