Skip to main content

Advertisement

SpringerLink
Log in

Prognostic scores for evaluating the survival benefit of regorafenib or trifluridine/tipiracil in patients with metastatic colorectal cancer: an exploratory analysis of the REGOTAS study

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Although regorafenib or trifluridine/tipiracil (FTD/TPI) has been recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC), not all patients have beneficial outcomes. This study aimed to develop a prognostic scoring system for evaluating the overall survival (OS) benefit.

Methods

Patients included in the REGOTAS study, which comprised 489 patients (regorafenib group: 199; FTD/TPI group: 290 patients), were evaluated. OS was analyzed using multivariate Cox proportional model. The prognostic score was calculated using the worst four individual factors weighted by hazard ratio, and the total scores were categorized as low-, moderate-, and high-OS benefit.

Results

The worst four factors in the regorafenib group were AST > 40 IU/dL (point, + 3), CRP ≥ 1.0 mg/dL (+ 2), number of metastatic organ site ≥ 3 (+ 2), and duration from initiation of 1st-line chemotherapy < 18 months (+ 2), while they were AST (+ 2), CRP (+ 2), CA19-9 > 37.0 U/mL (+ 2), and ECOG PS ≥ 1 (+ 2) in the FTD/TPI group. These corresponded to a total prognostic score of > 5, 2–4, and 0 points in the regorafenib group and 8, 2–6, and 0 points in the FTD/TPI group. The median OS in the low, moderate, and high OS benefit group was 3.3 (95% CI 3.0–3.7), 8.1 (95% CI 6.4–9.7), and 12.6 months (95% CI 10.6–14.6) in the regorafenib group and 2.8 (95% CI 2.0–3.5), 7.5 (95% CI 6.6–8.3), and 15.4 months (95% CI 9.7–21.2) in the FTD/TPI group.

Conclusion

These prognostic scores are useful for identifying patients with mCRC who will obtain survival benefits from these drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Modest DP, Pant S, Sartore-Bianchi A (2019) Treatment sequencing in metastatic colorectal cancer. Eur J Cancer 109:70–83

    Article  CAS  Google Scholar 

  2. Grothey A, Van Cutsem E, Sobrero A et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381(9863):303–312

    Article  CAS  Google Scholar 

  3. Mayer RJ, Van Cutsem E, Falcone A et al (2015) Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 372(20):1909–1919

    Article  Google Scholar 

  4. Sueda T, Sakai D, Kudo T et al (2016) Efficacy and safety of regorafenib or TAS-102 in patients with metastatic colorectal cancer refractory to standard therapies. Anticancer Res 36(8):4299–4306

    PubMed  CAS  Google Scholar 

  5. Masuishi T, Taniguchi H, Hamauchi S et al (2017) Regorafenib versus trifluridine/tipiracil for refractory metastatic colorectal cancer: a retrospective comparison. Clin Colorectal Cancer 16(2):e15–e22

    Article  Google Scholar 

  6. Unseld M, Drimmel M, Siebenhuner A et al (2018) Optimizing treatment sequence for late-line metastatic colorectal cancer patients using trifluridine/tipiracil and regorafenib. Clin Colorectal Cancer 17(4):274–279

    Article  Google Scholar 

  7. Moriwaki T, Fukuoka S, Taniguchi H et al (2018) Propensity score analysis of regorafenib versus trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy (REGOTAS): a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study. Oncologist 23(1):7–15

    Article  CAS  Google Scholar 

  8. Yamaguchi K, Komatsu Y, Satoh T et al (2019) Large-scale, prospective observational study of regorafenib in Japanese patients with metastatic colorectal cancer in a real-world clinical setting. Oncologist 24:e450–e457

    Article  CAS  Google Scholar 

  9. Cremolini C, Rossini D, Martinelli E et al (2018) Trifluridine/tipiracil (TAS-102) in refractory metastatic colorectal cancer: a multicenter register in the frame of the Italian Compassionate Use Program. Oncologist 23(10):1178–1187

    Article  CAS  Google Scholar 

  10. Shibutani M, Nagahara H, Fukuoka T et al (2019) Prognostic significance of the C-reactive protein-to-albumin ratio in patients with metastatic colorectal cancer treated with trifluridine/thymidine phosphorylase inhibitor as later-line chemotherapy. Anticancer Res 39(2):1051–1057

    Article  Google Scholar 

  11. Tsuchihashi K, Ito M, Moriwaki T et al (2018) Role of predictive value of the modified Glasgow Prognostic Score for later-line chemotherapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer 17(4):e687–e697

    Article  Google Scholar 

  12. Adenis A, de la Fouchardiere C, Paule B et al (2016) Survival, safety, and prognostic factors for outcome with regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 16:412

    Article  CAS  Google Scholar 

  13. Riedl JM, Posch F, Moik F et al (2017) Inflammatory biomarkers in metastatic colorectal cancer: prognostic and predictive role beyond the first line setting. Oncotarget 8(56):96048–96061

    Article  Google Scholar 

  14. Skuja E, Gerina-Berzina A, Hegmane A et al (2018) Duration of previous treatment as a prognostic factor in metastatic colorectal cancer treated with trifluridine/tipiracil. Mol Clin Oncol 8(5):699–702

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Song A, Eo W, Lee S (2015) Comparison of selected inflammation-based prognostic markers in relapsed or refractory metastatic colorectal cancer patients. World J Gastroenterol 21(43):12410–12420

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by funding from the JSCCR. We would like to thank Editage (https://www.editage.jp) for English language editing.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan

    Toshikazu Moriwaki

  2. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan

    Shota Fukuoka

  3. Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan

    Toshiki Masuishi

  4. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan

    Atsuo Takashima

  5. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan

    Yosuke Kumekawa

  6. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan

    Takeshi Kajiwara

  7. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Kentaro Yamazaki

  8. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Taito Esaki

  9. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan

    Akitaka Makiyama

  10. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan

    Tadamichi Denda

  11. Department of Medical Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan

    Yukimasa Hatachi

  12. Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan

    Takeshi Suto

  13. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan

    Naotoshi Sugimoto

  14. Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan

    Masanobu Enomoto

  15. Department of Specialized Surgeries, Tokyo Medical and Dental University, Graduate School of Medicine and Dentistry, Tokyo, Japan

    Toshiaki Ishikawa

  16. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Tomomi Kashiwada

  17. Department Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Eiji Oki

  18. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Hokkaido, Japan

    Yoshito Komatsu

  19. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Akihito Tsuji

  20. Department of Medicine and Biosystemic Science, Kyushu University Graduate of Medical Sciences, Fukuoka, Japan

    Kenji Tsuchihashi

  21. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan

    Daisuke Sakai

  22. Department of Surgery, National Defense Medical College Hospital, Saitama, Japan

    Hideki Ueno

  23. Department of Medical Oncology, Kindai University, Faculty of Medicine, Osaka, Japan

    Takao Tamura

  24. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan

    Kimihiro Yamashita

  25. Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Japan

    Yasuhiro Shimada

Authors
  1. Toshikazu Moriwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shota Fukuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshiki Masuishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsuo Takashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yosuke Kumekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeshi Kajiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kentaro Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Taito Esaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akitaka Makiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tadamichi Denda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yukimasa Hatachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takeshi Suto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Naotoshi Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masanobu Enomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Toshiaki Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Tomomi Kashiwada
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Eiji Oki
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yoshito Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Akihito Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Kenji Tsuchihashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Daisuke Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Hideki Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Takao Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Kimihiro Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Yasuhiro Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshikazu Moriwaki.

Ethics declarations

Conflict of interest

Atsuo Takashima received a research grant from Takeda, MSD, LSK, and Sumitomo Dainippon. Kentaro Yamazaki received honoraria from Taiho and Bayer, and a research grant from Taiho. Taito Esaki received honoraria from Lilly, and a research grant from Astellas, MSD, Dai-ichi-Sankyo, Ono, Merck Serono, Dainippon Sumitomo, Novartis, Taiho, and Lilly, and scholarship donations from Ono. Naotoshi Sugimoto received a research grant from MSD, Ono, Astellas, Dai-ichi Sankyo. Eiji Oki received honoraria from Taiho and Bayer. Yoshito Komatsu received honoraria from Lilly, Taiho, Chugai, Takeda, Bayer, Bristol Myers, Sanofi, Merck Serono, Yakult, and MSD, and a research grant from NanoCarrier, Baxter, Linical, QuintilesIMS, Sysmex, Mediscience, Ono, Dainippon Sumitomo, MSD, Taiho, Dai-ichi-Sankyo, and Yakult, and scholarship donations from Taiho, Chugai, Kyowa Kirin, Takeda, and Ono. Akihito Tsuji received honoraria from Taiho, Chugai, Takeda, Merck Serono, Lilly, Sanofi, and Bristol, and a research grant from Bristol Meyer, Ono, Taiho, and Sanofi. Daisuke Sakai received honoraria from Chugai, and a research grant from Lilly, Ono, Dai-ichi-Sankyo, and Astellas, and endowed chairs from Yakult, Chugai, and Ono. Hideki Ueno received a research grant from Taiho, Yakult, Bayer, Chugai, and Sysmex. Yasuhiro Shimada received a research grant from Taiho, MSD, and Lilly. All other authors declare no potential conflict of interest.

Ethical approval

The present study was approved from the Ethics Committee of the JSCCR. The requirement for informed consent was waived because of the retrospective design of this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moriwaki, T., Fukuoka, S., Masuishi, T. et al. Prognostic scores for evaluating the survival benefit of regorafenib or trifluridine/tipiracil in patients with metastatic colorectal cancer: an exploratory analysis of the REGOTAS study. Int J Clin Oncol 25, 614–621 (2020). https://doi.org/10.1007/s10147-019-01600-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-019-01600-0

Keywords

Search

Navigation