Michel Ducreux1, Lone Nørgård Petersen2, Leopold Öhler3, Francesca Bergamo4, Jean-Philippe Metges5, Jan Willem de Groot6, Jaw-Yuan Wang7, Beatriz García Paredes8, Emmanuelle Dochy9, Sabine Fiala-Buskies10, Andrés Cervantes11, Juan Manuel O'Connor12, Alfredo Falcone13. 1. Gastrointestinal Oncology Unit, Gustave Roussy Cancer Campus Grand Paris, Université Paris-Saclay, Villejuif, France. Electronic address: Michel.Ducreux@gustaveroussy.fr. 2. Department of Oncology, Rigshospitalet, Copenhagen, Denmark. 3. Internal Medicine I, Department of Oncology, St. Josef Krankenhaus, Vienna, Austria. 4. Medical Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy. 5. Service d'Oncologie et de Radiothérapie, CHU de Brest - Hôpital Morvan, ARPEGO Network, Brest, France. 6. Isala Oncology Center, Zwolle, Netherlands. 7. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan. 8. Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain. 9. Global Medical Affairs Oncology, Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 10. Medical Affairs Statistics and Integrated Analysis, Bayer AG, Wuppertal, Germany. 11. Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. 12. Department of Clinical Oncology, Institute Alexander Fleming, Buenos Aires, Argentina. 13. Department of Medical Oncology, University of Pisa, Pisa, Italy.
Abstract
BACKGROUND: Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. METHODS: The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). RESULTS: A total of 1037 patients were treated. The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand-foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0). CONCLUSIONS: In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. TRIAL REGISTRATION: NCT02042144.
BACKGROUND:Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. METHODS: The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). RESULTS: A total of 1037 patients were treated. The median age was 65 years (range: 24-93); 87% of patients had Eastern Cooperative Oncology Group performance status 0-1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand-foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2-8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8-3.0). CONCLUSIONS: In this real-world, observational study of patients with mCRC, the regorafenibtoxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. TRIAL REGISTRATION: NCT02042144.
Authors: Alena Novakova-Jiresova; Katerina Kopeckova; Ludmila Boublikova; Renata Chloupkova; Bohuslav Melichar; Lubos Petruzelka; Jindrich Finek; Ondrej Fiala; Peter Grell; Stanislav Batko; Zdenek Linke; Igor Kiss; Jana Prausova; Tomas Buchler Journal: Cancer Manag Res Date: 2020-07-03 Impact factor: 3.989