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Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study

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Abstract

Aim

To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib.

Methods

We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients.

Results

There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6–37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3–8.5) and 7.7 months (95% CI:6.6–8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7–3.9) and 3.5 months (95% CI: 3.0–4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77–1.28; p = 0.963 for OS; HR, 0.93; 0.77–1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group.

Conclusion

This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

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Data availability

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Abbreviations

AEs:

Adverse events

ATP:

Adenosine triphosphate

CI:

Confidence interval

CYP:

Cytochrome P450

CTCAE:

Common Terminology Criteria for Adverse Events

DDI:

Drug-drug interactions

ECOG:

Eastern Cooperative Oncology Group

GIST:

Gastrointestinal stromal tumor

HCC:

Hepatocellular cancer

IQR:

Interquartile range

mCRC:

Metastatic colorectal cancer

ORR:

Objective response rates

OS:

Overall survival

PPI(s):

Proton pump inhibitor(s)

RECIST:

Response evaluation criteria in solid tumors

TKIs:

Tyrosine kinase inhibitors

TTF:

Time to treatment failure

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Author information

Authors and Affiliations

  1. Department of Medical Oncology, Faculty of Medicine, Ankara University, 06590, Ankara, Turkey

    Emre Yekedüz, Yüksel Ürün & Güngör Utkan

  2. Cancer Research Institute, Ankara University, Ankara, Turkey

    Emre Yekedüz, Yüksel Ürün & Güngör Utkan

  3. Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey

    Mehmet Fatih Özbay & Hasan Şenol Coşkun

  4. Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Dilek Çağlayan & Mehmet Artaç

  5. Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Atila Yıldırım & Feyyaz Özdemir

  6. Department of Medical Oncology, University Faculty of Medicine, Faculty of Medicine Ankara, Ankara Yıldırım Beyazıt University, Ankara, Turkey

    Cihan Erol & Mehmet Ali Nahit Şendur

  7. Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Hasan Çağrı Yıldırım, Saadettin Kılıçkap & Şuayib Yalçın

  8. Department of Medical Oncology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey

    Sezai Tunç & Abdurrahman Işıkdoğan

  9. Medical Oncology Clinic, Prof. Dr. İlhan Özdemir State Hospital, Giresun, Turkey

    Neslihan Özyurt

  10. Faculty of Medicine, Liv Hospital Medical Oncology Clinic, İstinye University, Ankara, Turkey

    Saadettin Kılıçkap

Authors
  1. Emre Yekedüz
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  2. Mehmet Fatih Özbay
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  13. Yüksel Ürün
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  17. Güngör Utkan
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Contributions

Emre Yekedüz: Conceptualization, data curation, methodology, visualization, formal analysis, writing–original draft. Mehmet Fatih Özbay: Data curation, writing–review and editing. Dilek Çağlayan: Data curation, writing–review and editing. Atila Yıldırım: Data curation, writing–review and editing. Cihan Erol: Data curation, writing–review and editing. Hasan Çağrı Yıldırım: Data curation, writing–review and editing. Sezai Tunç: Data curation, writing–review and editing. Neslihan Özyurt: Data curation, writing–review and editing. Feyyaz Özdemir: Writing–review and editing, Supervision. Mehmet Ali Nahit Şendur: Writing, review and editing; supervision. Abdurrahman Işıkdoğan: Writing, review and editing; supervision. Saadettin Kılıçkap: Writing, review and editing; supervision. Yüksel Ürün: Methodology, Writing, review and editing; supervision. Şuayib Yalçın: Writing, review and editing; supervision. Mehmet Artaç: Writing, review and editing; supervision. Hasan Şenol Coşkun: Writing, review and editing; supervision. Güngör Utkan: Conceptualization, methodology, data curation, writing (review and editing), supervision.

Corresponding author

Correspondence to Emre Yekedüz.

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Competing interests

The authors declare no competing interests.

Ethics approval

This study was approved by the Ankara University Faculty of Medicine Human Research Ethics Committee, approval number İ9-601-21.

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Waiver of informed consent was obtained from the Research Ethics Board due to the minimal risk to study subjects as well as the retrospective nature of this study.

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Not applicable.

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The authors declare no competing interests.

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Yekedüz, E., Özbay, M.F., Çağlayan, D. et al. Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study. Eur J Clin Pharmacol 78, 1973–1979 (2022). https://doi.org/10.1007/s00228-022-03403-1

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