REVERCE: A Randomized Phase II Study of Regorafenib Followed by Cetuximab Versus the Reverse Sequence for Previously Treated Metastatic Colorectal Cancer Patients
Mené sur 101 patients atteints d'un cancer colorectal de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie globale, du régorafénib avant le cétuximab, par rapport à la séquence chronologique de référence
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 (mCRC) patients. Patients and methods : Patients with KRAS exon 2 wild-type mCRC after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence (cetuximab ± irinotecan followed by regorafenib; C-R arm). The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life (QOL). Exploratory endpoints included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA (ctDNA) 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 = 0.0293), with a hazard ratio (HR) of 0.61 for OS (95% 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 QOL 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 regorafenib. Conclusions : The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.
Annals of Oncology 2018