Abstract
Abstract
Background
Regorafenib and anti-EGFR monoclonal antibodies are standard therapies for RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC) in the refractory setting, but the optimal sequencing remains unknown. Herein, we report results from REVERCE II, a randomized phase II trial evaluating the efficacy and safety of sequencing these therapies.
Methods
Patients with RAS WT mCRC previously treated with fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive (R-E) regorafenib followed by anti-EGFR therapy ± irinotecan or (E-R) anti-EGFR therapy ± irinotecan followed by regorafenib sequentially. The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) with initial (PFS1) and second treatment (PFS2), sequential treatment PFS (stPFS), objective response rate (ORR), and safety. Exploratory endpoints included serial biomarker analyses. Unfortunately, the trial was closed prematurely due to slow enrollment and lack of funding.
Results
Twenty-two patients were enrolled (R-E: n = 12;E-R: n = 10) with sequential treatment initiated in 33% (4/12) and 80% (8/10) of patients in R-E and E-R, respectively. Median OS for R-E and E-R was 21.9 and 13.3 months, respectively (one-sided P = 0.114). PFS1 was 2.5 (R-E) vs. 5.6 months (E-R) (one-sided p = 0.998), while PFS2 was 3.7 vs. 2.0 months (one-sided p = 0.086). stPFS was similar (9.3 vs. 9.6 months; one-sided p = 0.358). ORR for initial treatment were 0% in R-E and 20% (2/8) in E-R. Sequential treatment ORR was 25% (n = 1/4) in R-E and 0% in E-R. No observed significant differences in adverse effects between arms.
Conclusion
While the study was closed prematurely prior to completion, the sequence of regorafenib prior to anti-EGFR therapy suggested a possible survival benefit. Further studies may help better determine the optimal treatment sequencing strategy in refractory mCRC.