REVERCE: a randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients

Abstract

557 (oral presentation in rapid fire abstract session). Translational research results were presented in poster discussion session of the Annual Meeting of the American Society of Clinical Oncology 2018 (1-5 June), and results of quality of life assessment were presented in poster discussion session of the European Society of Medical Oncology World Congress on Gastrointestinal Cancer 2018 (20-23 June). Background: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. Patients and methods: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab 6 irinotecan (R-C arm), or the reverse sequence [cetuximab 6 irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. Results: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P ¼ 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. Conclusions: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.

A multicentre, prospective study of plasma circulating tumour DNA test for detecting RAS mutation in patients with metastatic colorectal cancer

“…Patients who had received prior treatment with anti-EGFR antibodies or regorafenib were excluded according to the possible appearance of acquired resistant mutations. [9][10][11] This study was approved by the ethics committees at each institution (National Cancer Center Institutional Review Board, Kansai Rosai Hospital Review Board, Saitama Cancer Center Review Board, Chiba Cancer Center Review Board, National Hospital Organization Shikoku Cancer Center Review Board, Hokkaido University Review Board, Kyushu University Review Board, and Osaka University Review Board), and all patients provided written informed consent. All procedures related to the study were performed in accordance with the Helsinki Declaration.…”

Treatment of Rectal Cancer-Induced Disseminated Carcinomatosis of the Bone Marrow with FOLFOX plus Cetuximab and Panitumumab

“…However, effective reintroduction of oxaliplatin and anti-EGFR agents has been limited to patients treated for a duration of 6 months because of discontinuation and reintroduction in these reports. Recently, the REVERCE Study demonstrated that anti-EGFR treatment after regorafenib prolonged the overall survival more than the current standard sequence of treatment with an anti-EGFR agent followed by regorafenib [21]. Furthermore, preclinically, Napolitano et al [22] reported that regorafenib overcame anti-EGFR antibody resistance of colorectal cancer by blocking the mitogen-activated protein kinase (MAPK) and AKT pathways.…”

Regorafenib in Patients with Antiangiogenic-Naïve and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial

“…An exploratory subgroup analysis suggested that patients who had not received prior targeted therapy (including bevacizumab) had better outcomes with regorafenib than those who had received at least one prior targeted agent [11]. These results, together with more recent evidence [12], suggest that regorafenib treatment prior to targeted therapy may further improve outcomes in patients with mCRC. The current study was designed to investigate the efficacy and safety of regorafenib in patients with antiangiogenic therapynaïve chemotherapy-refractory mCRC.…”