Emre Yekedüz1,2, Mehmet Fatih Özbay3, Dilek Çağlayan4, Atila Yıldırım5, Cihan Erol6, Hasan Çağrı Yıldırım7, Sezai Tunç8, Neslihan Özyurt9, Feyyaz Özdemir5, Mehmet Ali Nahit Şendur6, Abdurrahman Işıkdoğan8, Saadettin Kılıçkap7,10, Yüksel Ürün11,12, Şuayib Yalçın7, Mehmet Artaç4, Hasan Şenol Coşkun3, Güngör Utkan11,12. 1. Department of Medical Oncology, Faculty of Medicine, Ankara University, 06590, Ankara, Turkey. emreyekeduz@gmail.com. 2. Cancer Research Institute, Ankara University, Ankara, Turkey. emreyekeduz@gmail.com. 3. Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. 4. Department of Medical Oncology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey. 5. Department of Medical Oncology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 6. Department of Medical Oncology, University Faculty of Medicine, Faculty of Medicine Ankara, Ankara Yıldırım Beyazıt University, Ankara, Turkey. 7. Department of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. 8. Department of Medical Oncology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey. 9. Medical Oncology Clinic, Prof. Dr. İlhan Özdemir State Hospital, Giresun, Turkey. 10. Faculty of Medicine, Liv Hospital Medical Oncology Clinic, İstinye University, Ankara, Turkey. 11. Department of Medical Oncology, Faculty of Medicine, Ankara University, 06590, Ankara, Turkey. 12. Cancer Research Institute, Ankara University, Ankara, Turkey.
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.
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.
Authors: Roelof W F van Leeuwen; Frank G A Jansman; Nicole G Hunfeld; Robert Peric; Anna K L Reyners; Alex L T Imholz; Jacobus R B J Brouwers; Joachim G Aerts; Teun van Gelder; Ron H J Mathijssen Journal: Clin Pharmacokinet Date: 2017-07 Impact factor: 6.447