RT Journal Article
T1 Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial).
A1 Garcia-Alfonso, Pilar
A1 Benavides, Manuel
A1 Falco, Esther
A1 Muñoz, Andres
A1 Gomez, Auxiliadora
A1 Sastre, Javier
A1 Rivera, Fernando
A1 Montagut, Clara
A1 Salgado, Mercedes
A1 Lopez-Ladron, Amelia
A1 Lopez, Rafael
A1 Ruiz de Mena, Inmaculada
A1 Duran, Gema
A1 Aranda, Enrique
K1 Área de Gestión Sanitaria Sur de Sevilla
K1 Antineoplastic agents, immunological
K1 Antineoplastic combined chemotherapy protocols
K1 Bevacizumab
K1 Camptothecin
K1 Colorectal neoplasms
AB RAS- or BRAF-mutated metastatic colorectal cancers (mCRCs) progressing after first-line treatment have a poor prognosis.European and U.S. guidelines include the multikinase inhibitor regorafenib as a standard option for second-line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival.Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second-line treatment for patients with mCRC bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the population analyzed. Patients with RAS- or BRAF-mutated (mut) metastatic colorectal cancer (mCRC) progressing on first-line bevacizumab plus 5-FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess the efficacy and safety of regorafenib in this population. Regorafenib was administered daily for 3 weeks of each 4-week cycle until disease progression or other reason. The primary endpoint was 6-month progression-free survival (PFS). KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and 13% of patients, respectively. Median time from initial diagnosis of metastases to the start of regorafenib and treatment duration was 13.8 months and 7 weeks, respectively. Reasons for discontinuation included disease progression (80%), investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%) required dose reduction, mostly for asthenia (43%). The most common regorafenib-related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%) (Table 1). There were no grade 4 toxicities. No patient was progression-free at 6 months. Median PFS, time to progression (TTP), and overall survival (OS) were 2.2, 2.0, and 3.3 months, respectively. Although stopped prematurely for failing to accrue, in the population analyzed, regorafenib failed to demonstrate clinical activity in KRAS- or BRAF-mutated mCRC with progression following first-line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier line of therapy should not be undertaken without better population refinement.
PB Oxford University Press
YR 2018
FD 2018-05-28
LK http://hdl.handle.net/10668/12849
UL http://hdl.handle.net/10668/12849
LA en
NO García-Alfonso P, Benavides M, Falcó E, Muñoz A, Gómez A, Sastre J, et al. Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial). Oncologist. 2018 Nov;23(11):1271-e128
DS RISalud
RD Apr 10, 2025