Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

Guillem Argilés, Mark P Saunders, Fernando Rivera, Alberto Sobrero, Al Benson, Carmen Guillén Ponce, Stefano Cascinu, Eric Van Cutsem, Iain R Macpherson, Dirk Strumberg, Claus-Henning Köhne, John Zalcberg, Andrea Wagner, Vittorio Luigi Garosi, Julia Grunert, Josep Tabernero, Fortunato Ciardiello

Journal: European journal of cancer (Oxford, England : 1990) 2015;51(8):942-9

PMID: 25818084

Free Full Text on Institutional Repository of University of Modena and Reggio Emilia (IRIS UNIMORE) View on PubMed

Abstract

BACKGROUND

The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC.

METHODS

In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety.

RESULTS

Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications.

CONCLUSION

Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone.

Address: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Electronic address: [email protected].; The Christie, 550 Wilmslow Road, Manchester M20 4BX, UK. Electronic address: [email protected].; University Hospital 'Marqués de Valdecilla', Avda. De Valdecilla 25, 39008 Santander Cantabria, Spain. Electronic address: [email protected].; IRCCS San Martino IST Hospital, Largo Rosanna Benzi 10, Genova 16132, Italy. Electronic address: [email protected].; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N. St. Clair, Suite 850, Chicago, IL 60611, USA. Electronic address: [email protected].; University Hospital Ramón y Cajal, Carretera de Colmenar Viejo, km. 9,100, 28034 Madrid, Spain. Electronic address: [email protected].; University Hospital Riuniti Umberto I, Via Conca, 60126 Ancona, Italy. Electronic address: [email protected].; University Hospitals and KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: [email protected].; Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. Electronic address: [email protected].; University Hospitals, Marienhospital Herne, Hölkeskampring 40, 44625 Herne, Germany. Electronic address: [email protected].; Oldenburg Clinic, Rahel-Straus-Straße 10, 26133 Oldenburg, Germany. Electronic address: [email protected].; School of Public Health and Preventive Medicine Faculty of Medicine, Nursing and Health Sciences, Monash University, The Alfred Centre, 99 Commercial Rd, Melbourne 3004, Australia. Electronic address: [email protected].; Bayer Pharma AG, Müllerstraße 178, 13353 Berlin, Germany. Electronic address: [email protected].; Bayer S.p.A., Viale Certosa 210, 20156 Milan, Italy. Electronic address: [email protected].; Bayer Pharma AG, Aprather Weg 18, 42096 Wuppertal, Germany. Electronic address: [email protected].; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.; Second University Hospital, Via S Pansini 5, 80131 Naples, Italy. Electronic address: [email protected].

DOI: 10.1016/j.ejca.2015.02.013

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MeSH Terms: Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms, Female, Fluorouracil, Historically Controlled Study, Humans, Leucovorin, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Metastasis, Organoplatinum Compounds, Phenylurea Compounds, Pyridines, Treatment Outcome