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Neutropenia is an indicator of outcomes in metastatic colorectal cancer patients treated with FTD/TPI plus bevacizumab: a retrospective study

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Abstract

Purpose

Trifluridine/tipiracil (FTD/TPI) improves the overall survival (OS) of metastatic colorectal cancer (mCRC) patients. Additionally, FTD/TPI plus bevacizumab (BEV) has demonstrated promising efficacy for mCRC patients who are refractory to standard chemotherapy. Chemotherapy-induced neutropenia (CIN) has been reported to be an indicator of efficacy for FTD/TPI. This study investigated whether CIN was an indicator of efficacy for FTD/TPI plus BEV.

Methods

We reviewed chemo-refractory mCRC patients who were treated with FTD/TPI alone (monotherapy) or FTD/TPI plus BEV (combination) at our institution and compared the safety and efficacy of the two. Progression-free survival (PFS) and OS were analyzed using Kaplan–Meier curves. We also investigated correlations between CIN and outcomes.

Results

In total, 56 patients received FTD/TPI, among whom 24 and 32 were treated with monotherapy and combination therapy, respectively. The median PFS was 1.8 and 4.7 months for the monotherapy and combination arms, respectively (hazard ratio [HR]: 0.28; 95% confidence interval [CI]: 0.15–0.51; P < 0.001). The median OS was 6.3 and 11.7 months for the monotherapy and combination arms, respectively (HR 0.25; 95% CI 0.13–0.48; P < 0.001). CIN (Grade 3 or worse) developed in five (20.8%) and 17 (53.1%) patients from the monotherapy and combination arms, respectively (P = 0.030). Patients with CIN in the combination arm had improved PFS and OS compared with non-CIN patients (P = 0.033 and P = 0.045, respectively).

Conclusions

FTD/TPI plus BEV prolonged PFS and OS and had tolerable toxicity compared with FTD/TPI alone. CIN is an indicator of patients who will benefit from FTD/TPI plus BEV.

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Abbreviations

FTD/TPI:

Trifluridine/tipiracil

BEV:

Bevacizumab

mCRC:

Metastatic colorectal cancer

CIN:

Chemotherapy-induced neutropenia

Monotherapy:

FTD/TPI alone

Combination:

FTD/TPI plus BEV

CI:

Confidence interval

OS:

Overall survival

PFS:

Progression-free survival

CTCAE:

Common Terminology Criteria for Adverse Events

ECOG:

Eastern Cooperative Oncology Group

PS:

Performance status

G-CSF:

Granulocyte colony-stimulating factor

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Acknowledgements

We thank James P. Mahaffey, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Department of Surgery, Japan Organization of Occupational Health and Safety, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan

    Yohei Nose, Yoshinori Kagawa, Taishi Hata, Ryota Mori, Kenji Kawai, Atsushi Naito, Takuya Sakamoto, Kohei Murakami, Yoshiteru Katsura, Yoshiaki Ohmura, Toru Masuzawa, Atsushi Takeno, Yutaka Takeda, Takeshi Kato & Kohei Murata

  2. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Yohei Nose & Ryota Mori

  3. Department of Surgery, Osaka Police Hospital, Osaka, Japan

    Atsushi Naito

  4. Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan

    Takeshi Kato

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  1. Yohei Nose
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  2. Yoshinori Kagawa
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Corresponding author

Correspondence to Yoshinori Kagawa.

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Conflict of interest

Yoshinori Kagawa received reports lecture fee from Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin Japan, Eli Lilly, Yakult Honsha Co., Ltd., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. and Merck Biopharma Co., Ltd. Takeshi Kato reports receiving honoraria from ONO Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd, Bayer Yakuhin Japan and Boehringer-Ingelheim, receiving research funding from Chugai Pharmaceutical Co, and Takeda Pharmaceutical Co. outside the submitted work. The other authors declare that they have no conflict of interest.

Ethical approval

The study data and informed consent were obtained from all individual participants included in the study in accordance with the Declaration of Helsinki and were approved by the Ethics Review Board of our institution (registration number: 1901020).

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This article does not contain any studies with animals performed by any of the authors.

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Nose, Y., Kagawa, Y., Hata, T. et al. Neutropenia is an indicator of outcomes in metastatic colorectal cancer patients treated with FTD/TPI plus bevacizumab: a retrospective study. Cancer Chemother Pharmacol 86, 427–433 (2020). https://doi.org/10.1007/s00280-020-04129-6

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  • DOI: https://doi.org/10.1007/s00280-020-04129-6

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