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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)

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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.

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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

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Acknowledgements

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

Author information

Authors and Affiliations

  1. First Department of Medicine, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Yasuyuki Ikezawa, Hajime Asahina, Satoshi Oizumi, Megumi Furuta, Jun Sakakibara-Konishi & Masaharu Nishimura

  2. Department of Respiratory Medicine, Oji General Hospital, 3-4-8 Wakakusa-cho, Tomakomai, Hokkaido, 053-8506, Japan

    Yasuyuki Ikezawa & Yasutaka Kawai

  3. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, 2-3-54 Kikusui 4, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan

    Satoshi Oizumi, Masahiro Watanabe & Noriyuki Yamada

  4. Department of Respiratory Medicine, Obihiro-Kosei General Hospital, 1 West 6, North 8, Obihiro, Hokkaido, 080-0016, Japan

    Kei Takamura & Takahiro Ogi

  5. Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 2 West 7, 9-jo, Iwamizawa, Hokkaido, 068-8555, Japan

    Noriyuki Yamada

  6. Center for Respiratory Diseases, JCHO Hokkaido Hospital, 3-18, 8-chome, Nakanoshima 1-jo, Sapporo, Hokkaido, 062-8618, Japan

    Toshiyuki Harada

  7. Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Ichiro Kinoshita, Toraji Amano & Hirotoshi Dosaka-Akita

  8. Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, 7-4048 Hanasaki-cho, Asahikawa, Hokkaido, 070-8644, Japan

    Yuka Fujita

  9. Department of Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Eisaku Miyauchi

  10. Department of Translational Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Hiroshi Nishihara

  11. Department of Respiratory Medicine, KKR Sapporo Medical Center, 3-40, 6-chome, Hiragishi 1-jo, Toyohira-ku, Sapporo, Hokkaido, 062-0931, Japan

    Hiroshi Isobe

Authors
  1. Yasuyuki Ikezawa
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  2. Hajime Asahina
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  3. Satoshi Oizumi
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  4. Masahiro Watanabe
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  6. Yasutaka Kawai
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  7. Noriyuki Yamada
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  15. Jun Sakakibara-Konishi
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  17. Hirotoshi Dosaka-Akita
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  18. Hiroshi Isobe
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  19. Masaharu Nishimura
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on behalf of Hokkaido Lung Cancer Clinical Study Group

Corresponding author

Correspondence to Hajime Asahina.

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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.

Additional information

Hokkaido Lung Cancer Clinical Study Group: Clinical trial registration no. UMIN000005308.

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Ikezawa, Y., Asahina, H., Oizumi, S. et al. 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). Cancer Chemother Pharmacol 80, 955–963 (2017). https://doi.org/10.1007/s00280-017-3432-4

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