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Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study

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Abstract

Purpose

Although docetaxel plus ramucirumab has shown superior treatment efficacy over docetaxel monotherapy for patients with non-small cell lung cancer (NSCLC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to validate the primary prophylactic use of pegfilgrastim with docetaxel and ramucirumab treatment in Japanese patients with NSCLC.

Methods

Patients with NSCLC with progression after at least one round of chemotherapy were enrolled and administered docetaxel (60 mg/m2) plus ramucirumab (10 mg/kg) intravenously on day 1, followed by pegylated-granulocyte colony-stimulating factor (3.6 mg) on day 2 of a 21-day treatment cycle. The primary study endpoint was the percentage of patients who developed FN. Secondary endpoints included overall survival, progression-free survival, overall response rate, and safety.

Results

Overall, 20 patients (15 men and 5 women) were enrolled, of whom one developed FN, resulting in an overall FN rate of 5%. The response and disease control rates were 40% and 85%, respectively. The median progression-free survival was 6.6 (95% confidence interval [CI], 0.5-NR) months. The median overall survival was 18.4 (95% CI, 2.2–11.0) months. Six patients aged over 75 years were included in this study, and although most adverse events were durable, ramucirumab-associated adverse events occurred more frequently in these patients.

Conclusions

We observed a 5% FN rate using primary prophylactic pegylated-granulocyte colony-stimulating factor with docetaxel plus ramucirumab in Japanese patients with NSCLC. While most adverse events were durable, elderly patients should be closely monitored.

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Acknowledgments

The authors would like to thank Dr. Kazue Umezu from the Department of Respiratory Medicine, Gunma University Graduate School of Medicine along with Dr. Sho Osawa and Dr. Takashi Osaki for their valuable assistance in clinical work.

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Authors and Affiliations

  1. Innovative Medical Research Center, Gunma University Hospital, Maebashi, Gunma, 371-8511, Japan

    Norimitsu Kasahara & Takayuki Asao

  2. Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Noriaki Sunaga, Yusuke Tsukagoshi, Tomomi Masuda, Shinsuke Kitahara, Hiroaki Tsurumaki, Masakiyo Yatomi, Kenichiro Hara, Yasuhiko Koga & Toshitaka Maeno

  3. Department of Respiratory Medicine, Shibukawa Medical Center, Shibukawa, Gunma, Japan

    Tomohito Kuwako & Asuka Jingu

  4. Department of Respiratory Medicine, Hidaka Hospital, Takasaki, Gunma, Japan

    Ichiro Naruse

  5. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan

    Hisao Imai

  6. Oncology Center, Gunma University Hospital, Maebashi, Gunma, Japan

    Reiko Sakurai

  7. Clinical Research Center, Shizuoka Cancer Center, Nagaizumi, Shizuoka, Japan

    Keita Mori

  8. Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan

    Kyoichi Kaira

  9. Graduate School of Health Sciences, Gunma University, Maebashi, Gunma, Japan

    Takeshi Hisada

Authors
  1. Norimitsu Kasahara
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  2. Noriaki Sunaga
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  3. Tomohito Kuwako
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  4. Ichiro Naruse
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  5. Hisao Imai
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  17. Toshitaka Maeno
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  18. Takayuki Asao
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  19. Takeshi Hisada
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analyses were performed by Norimitsu Kasahara, Tomohito Kuwako, Hisao Imai, and Ichiro Naruse. The first draft of the manuscript was written by Norimitsu Kasahara and all authors contributed to editing the subsequent drafts of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Norimitsu Kasahara.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Research involving human participants

All procedures performed in this study involving human participants were in accordance with the institutional review board of Gunma University Hospital (protocol number 1499) and with the 1964 declaration of Helsinki and its later amendments or comparable ethical standards.

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

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Kasahara, N., Sunaga, N., Kuwako, T. et al. Administration of docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte colony-stimulating factor for pretreated non-small cell lung cancer: a phase II study. Support Care Cancer 28, 4825–4831 (2020). https://doi.org/10.1007/s00520-020-05317-z

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