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Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer

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Abstract

Purpose

Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf®), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. Here, we report the safety and tolerability profile of FTD/TPI from an expanded-access program (EAP) in the US patients with mCRC whose disease has progressed on the standard therapies.

Methods

A total of 549 patients (≥ 18 years) with histologically confirmed mCRC following two or more regimens of standard therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1 participated in this open-label EAP. During the 28-day treatment cycle, patients took FTD/TPI 35 mg/m2 twice daily for 5 days followed by 2 days of rest for 2 weeks, with a 14-day rest period. Data were collected for therapy duration, treatment discontinuation, and adverse events. Age-based post hoc analysis was performed to determine the safety of FTD/TPI in elderly (≥ 65 years) versus younger (< 65 years) patients.

Results

FTD/TPI-treated patients in this EAP had a similar therapy duration and time to treatment discontinuation to those in the RECOURSE trial. The safety profile in elderly patients was consistent with that in younger patients, with no unexpected safety concerns.

Conclusions

This USA-based, open-label EAP has confirmed a similar safety and tolerability profile for FTD/TPI to that observed in the RECOURSE trial. Furthermore, FTD/TPI is well tolerated and can be considered as a treatment option in elderly patients with mCRC.

Trial registration

NCT02286492.

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Abbreviations

AE:

Adverse event

EAP:

Expanded-access program

FTD/TPI:

Trifluridine/tipiracil

mCRC:

Metastatic colorectal cancer

SAE:

Serious adverse event

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Acknowledgements

The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. All authors contributed to the research, writing, and reviewing of all drafts of the manuscript and approved the final draft. Editorial support in the preparation of this publication was provided by Madeeha Aqil, Ph.D., at Complete HealthVizion, supported by Taiho Oncology, Inc. This study was funded by Taiho Oncology, Inc. Editorial support in the preparation of this publication was provided by Madeeha Aqil, Ph.D., at Complete HealthVizion, supported by Taiho Oncology, Inc.

Funding

This study was funded by Taiho Oncology, Inc.

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02115, USA

    Robert J. Mayer

  2. Yale Cancer Center, New Haven, CT, USA

    Howard S. Hochster

  3. Jefferson Health System/Abington Memorial Hospital, Abington, PA, USA

    Steven J. Cohen

  4. Taiho Oncology, Inc., Princeton, NJ, USA

    Robert Winkler

  5. Stathmi, Inc., New Hope, PA, USA

    Lukas Makris

  6. Mayo Clinic Cancer Center, Rochester, MN, USA

    Axel Grothey

Authors
  1. Robert J. Mayer
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  2. Howard S. Hochster
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  3. Steven J. Cohen
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  4. Robert Winkler
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  5. Lukas Makris
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  6. Axel Grothey
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Corresponding author

Correspondence to Robert J. Mayer.

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Conflict of interest

Robert J. Mayer has received honoraria from Taiho and consulting fees from Taiho and CASI Pharmaceuticals. Howard S. Hochster has received consulting fees from Bayer, Genentech, Amgen, and Merck. Steven J. Cohen has received consulting fees from Taiho, Bayer HealthCare Pharmaceuticals, Celgene, and Merrimack. Robert Winkler is employed by Taiho and has received leadership compensation and travel and accommodation support from Taiho. Lukas Makris is employed by Stathmi Inc. and is a statistical consultant for Taiho. Axel Grothey is employed by Mayo Clinic Cancer Center; Mayo Clinic Foundation has received consulting honoraria from Taiho and Bayer from his work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

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

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Mayer, R.J., Hochster, H.S., Cohen, S.J. et al. Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer. Cancer Chemother Pharmacol 82, 961–969 (2018). https://doi.org/10.1007/s00280-018-3686-5

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  • DOI: https://doi.org/10.1007/s00280-018-3686-5

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