PURPOSE: Regorafenib is an oral multikinase inhibitor approved for the therapy of previously treated metastatic colorectal carcinoma (mCRC). The aim of the present study was to analyze the outcomes of treatment with regorafenib in real-world clinical practice based on data from a national registry. METHODS: The CORECT registry, the Czech non-interventional database of patients with mCRC treated with targeted agents, searched for patients with metastatic CRC treated with regorafenib. In total, 555 evaluable patients were identified. RESULTS: The median age at diagnosis was 61.7 years. All patients had disease progression on or after previous systemic treatment. Most patients were treated with an initial dose of 160 mg daily (n = 463; 83.6%). The median duration of treatment was 2.7 months (range 0.0-23.4 months). By the data cut-off date, 472 patients (85%) had completed treatment with regorafenib and were evaluable for treatment response evaluation. Partial response was reported in 13 patients (2.8%) and disease stabilization in 130 patients (27.5%). Median progression-free survival (PFS) and overall survival (OS) were 3.5 months (95% confidence interval [CI] 3.2-3.7 months) and 9.3 months (95% CI 8.3-10.3 months), respectively. The 6-month OS rate was 67.7% (95% CI 63.4-72.1%). Multivariable analysis showed that female gender, longer interval from diagnosis of metastatic disease, M0 stage at diagnosis, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 were associated with longer PFS, while higher body-mass index (BMI), longer interval from diagnosis of metastatic disease, and ECOG PS of 0 were associated with longer OS. CONCLUSION: OS of patients treated with regorafenib in the real-world clinical practice in this cohort exceeded that reported in randomized trials. Regorafenib is a safe and active treatment option for a subgroup of patients with mCRC who are progressing after other systemic therapies and maintain good performance status.

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Oncology 1st Faculty of Medicine and Thomayer Hospital Charles University Prague Czech Republic

Department of Oncology and Radiotherapy Medical School and University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Oncology General Faculty Hospital Charles University Prague Czech Republic

Department of Oncology Palacky University Medical and Teaching Hospital Olomouc Czech Republic

Department of Oncology University Hospital in Motol Charles University Prague Czech Republic

Institute of Biostatistics and Analysis Faculty of Medicine Masaryk University Brno Czech Republic

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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi:10.3322/caac.21492 PubMed DOI

Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–1502. doi:10.1016/S0140-6736(13)61649-9 PubMed DOI

Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099–7109. doi:10.1158/0008-5472.CAN-04-1443 PubMed DOI

Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129(1):245–255. doi:10.1002/ijc.25864 PubMed DOI

Schmieder R, Hoffmann J, Becker M, et al. Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer. Int J Cancer. 2014;135(6):1487–1496. doi:10.1002/ijc.28669 PubMed DOI PMC

Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):9863. doi:10.1016/S0140-6736(12)61900-X PubMed DOI

Kopeckova K, Buchler T, Bortlicek Z, et al. Regorafenib in the real-life clinical practice: data from the Czech registry. Target Oncol. 2017;12(1):89–95. doi:10.1007/s11523-016-0458-1 PubMed DOI

Buchler T, Chloupkova R, Poprach A, et al. Sequential therapy with bevacizumab and EGFR inhibitors for metastatic colorectal carcinoma: a national registry-based analysis. Cancer Manag Res. 2019;11:359–368. doi:10.2147/CMAR.S183093 PubMed DOI PMC

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247. doi:10.1016/j.ejca.2008.10.026 PubMed DOI

Li J, Qin S, Xu R, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619–629. doi:10.1016/S1470-2045(15)70156-7 PubMed DOI

Adenis A, de la Fouchardiere C, Paule B, et al. 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. 2016;16(1):412. doi:10.1186/s12885-016-2440-9 PubMed DOI PMC

Van Cutsem E, Martinelli E, Cascinu S, et al. Regorafenib for patients with metastatic colorectal cancer who progressed after standard therapy: results of the large, single-arm, open-label phase IIIb CONSIGN study. Oncologist. 2019;24(2):185–192. doi:10.1634/theoncologist.2018-0072 PubMed DOI PMC

Mercier J, Voutsadakis IA. A systematic review and meta-analysis of retrospective series of regorafenib for treatment of metastatic colorectal cancer. Anticancer Res. 2017;37(11):5925–5934. doi:10.21873/anticanres.12039 PubMed DOI

Pietrantonio F, Miceli R, Rimassa L, et al. Estimating 12-week death probability in patients with refractory metastatic colorectal cancer: the colon life nomogram. Ann Oncol. 2017;28(3):555–561. doi:10.1093/annonc/mdw627 PubMed DOI

Grell P, Borilova S, Schwanzerova R, et al. Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC). J Clin Oncol. 2020;38(4_suppl):137. doi:10.1200/JCO.2020.38.4_suppl.137 PubMed DOI

Huemer F, Schlintl V, Hecht S, et al. Regorafenib is associated with increased skeletal muscle loss compared to TAS-102 in metastatic colorectal cancer. Clin Colorectal Cancer. 2019;18(2):159–166.e3. doi:10.1016/j.clcc.2019.04.003 PubMed DOI

Sasaki S, Oki E, Saeki H, et al. Skeletal muscle loss during systemic chemotherapy for colorectal cancer indicates treatment response: a pooled analysis of a multicenter clinical trial (KSCC 1605-A). Int J Clin Oncol. 2019;24(10):1204–1213. doi:10.1007/s10147-019-01460-8 PubMed DOI

Barret M, Antoun S, Dalban C, et al. Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer. Nutr Cancer. 2014;66(4):583–589. doi:10.1080/01635581.2014.894103 PubMed DOI

Bufill JA. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990;113(10):779–788. doi:10.7326/0003-4819-113-10-779 PubMed DOI

Iacopetta B. Predictive values of sex and tumour site for survival benefit from 5FU in colorectal cancer. Br J Cancer. 2002;86(9):1524–1526. doi:10.1038/sj.bjc.6600279 PubMed DOI PMC

Yamauchi M, Morikawa T, Kuchiba A, et al. Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut. 2012;61(6):847–854. doi:10.1136/gutjnl-2011-300865 PubMed DOI PMC

Price TJ, Beeke C, Ullah S, et al. Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease? Cancer. 2015;121(6):830–835. doi:10.1002/cncr.29129 PubMed DOI

Yang Y, Wang G, He J, et al. Gender differences in colorectal cancer survival: a meta-analysis. Int J Cancer. 2017;141(10):1942–1949. doi:10.1002/ijc.30827 PubMed DOI

Eker B, Ozaslan E, Karaca H, et al. Factors affecting prognosis in metastatic colorectal cancer patients. Asian Pac J Cancer Prev. 2015;16(7):3015–3021. doi:10.7314/apjcp.2015.16.7.3015 PubMed DOI

Kim S-E, Paik HY, Yoon H, Lee JE, Kim N, Sung M-K. Sex- and gender-specific disparities in colorectal cancer risk. World J Gastroenterol. 2015;21(17):5167–5175. doi:10.3748/wjg.v21.i17.5167 PubMed DOI PMC

Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28(3):466–474. doi:10.1200/JCO.2009.23.3452 PubMed DOI

Lech G, Slotwinski R, Slodkowski M, Krasnodebski IW. Colorectal cancer tumour markers and biomarkers: recent therapeutic advances. World J Gastroenterol. 2016;22(5):1745–1755. doi:10.3748/wjg.v22.i5.1745 PubMed DOI PMC

Ducreux M, Petersen LN, Ohler L, et al. Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational CORRELATE study. Eur J Cancer. 2019;123:146–154. doi:10.1016/j.ejca.2019.09.015 PubMed DOI

Bekaii-Saab TS, Ou F-S, Ahn DH, et al. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019;20(8):1070–1082. doi:10.1016/S1470-2045(19)30272-4 PubMed DOI PMC

Fedyanin M, Polyanskaya E, Pokataev I, Tryakin A, Tjulandin S. Started dose of regorafenib and overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): a systematic review and meta-analysis. J Clin Oncol. 2020;38(4_suppl):131. doi:10.1200/JCO.2020.38.4_suppl.131 DOI