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A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101)

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Abstract

Background

This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR.

Methods

Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4–6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL).

Results

Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1–6) and 4 (range 1–20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0–72.6%]. The ORR was 48.0% (95% CI 34.8–61.5%), and disease control rate was 86.0% (95% CI 73.8–93.0%). The median PFS and OS were 6.5 months (95% CI 5.8–7.2 months) and 21.4 months (95% CI 15.9–26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment.

Conclusions

Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR.

Trial registration

UMIN000005872.

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Acknowledgements

We thank all the patients, their families, and investigators who participated in this study.

Funding

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

Author information

Authors and Affiliations

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

    Taichi Takashina & Satoshi Oizumi

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

    Taichi Takashina, Hajime Asahina, Noriyuki Yamada & Masaharu Nishimura

  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, Noriyuki Yamada, Masao Harada, Hiroshi Yokouchi & Kosuke Nakano

  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 Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1247, Japan

    Hiroshi Yokouchi & Kenya Kanazawa

  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 Respiratory Medicine, Sapporo-Kosei General Hospital, 5 North 3, East 8, Sapporo, Hokkaido, 060-0033, Japan

    Osamu Honjo

  8. Division of Pulmonary Medicine, Allergy, and Rheumatology, Iwate Medical University School of Medicine, 1 Uchimaru 19, Morioka, Iwate, 020-0023, Japan

    Naoto Morikawa

  9. 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 & Hirotoshi Dosaka-Akita

  10. Department of Respiratory Medicine, Sapporo Higashi Tokushukai Hospital, 3-1, Kita 33-jo Higashi 14-chome, Higashi-ku, Sapporo, Hokkaido, 065-0033, Japan

    Ryoichi Honda

  11. Clinical Research and Medical Innovation Center, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Toraji Amano

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

    Hiroshi Isobe

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  1. Taichi Takashina
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  19. Masaharu Nishimura
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Hokkaido Lung Cancer Clinical Study Group

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Correspondence to Hajime Asahina.

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Takashina, T., Asahina, H., Oizumi, S. et al. A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101). Int J Clin Oncol 23, 1060–1069 (2018). https://doi.org/10.1007/s10147-018-1318-z

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  • DOI: https://doi.org/10.1007/s10147-018-1318-z

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