Safety analysis of regorafenib prior to selective internal radiation therapy (SIRT) using 90Y resin microspheres for the treatment (tx) of patients (pts) with refractory metastatic colorectal cancer (mCRC) with liver metastases (mets).

Abstract

e15040 Background: SIRT (or radioembolization) has been successfully used in the tx of mCRC patients with liver mets who are not surgical candidates. The addition of the multi-kinase inhibitor, regorafenib to SIRT is an attractive option as anti-tumor and maintenance tx for refractory CRC. Here we present the safety analysis of the 1st of 2 cohorts of our Phase II, open-label study comparing the safety of the combination of SIRT and regorafenib where chemotherapy occurs either before or after SIRT. Methods: mCRC pts with evidence of liver mets not treatable by surgical resection or local ablation were tx with 160 mg regorafenib QD PO on days 1-21 of a 28-day cycle followed by a 1 week (wk) washout then SIRT infusion (SIR-Spheres; Sirtex, North Sydney, Australia). Liver function was evaluated 2 wks and 4 wks after SIRT, and regorafenib was re-initiated if liver function was normal. Pts were evaluated for safety, and restaged on wk 6 and 12 following SIRT. The primary objective was to evaluate the safety of this tx schema. Results: 25 pts were enrolled from 7/15 to 8/16: median age 56 yrs, 48% male; 88% colon cancer, 12%, rectal cancer; 48% KRASmt, 4% BRAFmt. 68% of pts had prior systemic therapy for metastatic disease and 80% of pts had prior CRC surgeries. Pts received a median 11 wks regorafenib. 3 pts received regorafenib, but not SIRT due to disease progression. The median activity of SIRT delivered to the liver was 38 mCi and the median lung shunt fraction was 4%. The median tumor volume treated was 76 mL. The most common tx-related adverse events (AEs) were fatigue (60% all grades [G]; 8% G3/4), decreased appetite (32% all G; 0 G 3/4), and nausea (32%, all G; G 3/4). There were 4 tx-related serious AEs (bowel perforation, intractable abdominal pain, portal hypertension, and diarrhea) and no tx-related deaths. The overall response rate was 4%. The median PFS was 4 months and the median OS was 12 months. Conclusions: The treatment of mCRC pts with liver mets with regorafenib followed by SIRT infusion was found to be tolerable in this pt population. Further efficacy analysis of this treatment schema is merited. Clinical trial information: NCT02195011.