Long Term Survival With Regorafenib: Reality (Real Life In Italy) Trial A Giscad Study

Regorafenib (R) is a key agent for metastatic colorectal cancer (mCRC) treatment but no validated factors predicting longer survival are available. REALITY was a retrospective multicentric trial in Italian refractory mCRC patients (pts) reaching OS≥ 6 months (m) with R. We aimed to assess the association between clinical parameters and outcome in the study population to define a panel identifying long term survivors among R candidates. Primary and secondary endpoints were OS and PFS, respectively. Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier method; survival curves comparison: log-rank test). 100 R-treated mCRC pts from Jan 2014 to Dec 2015 with OS≥6 m were enrolled. Median OS was 11.5 m (95%CI 9,60-12,96). OS was longer in moderately differentiated (G2) mCRC (12,4 versus [vs] 7,4 vs 9,1 m G1 vs G3; p=0,0026) and for LDH levels ≤217 U/l (12,1 vs 8,7 m, p=0,0470). OS was improved with 160 mg starting dose at cycle 2 (12,4 vs 10,9 m 120 mg vs 9,1 m 80 mg, p=0,0325) and 4 (17,7 vs 12,1 m 120 mg vs 14,5 m 80 mg, p=0,0288), and in absence of adverse events (AE) over the first 4 cycles (22,5 vs 10,2 m, p=0,0018), cycle 1 (14,7 vs 10,7 m, p=0,0410) and 2 (15,6 vs 10,9 m, p=0,0474). OS was longer in absence of dose/schedule changes overall during the first 4 cycles (17,7 vs 10 m, p=0,0012), cycle 3 (14,7 vs 9,7 m, p=0,0031), and 4 (15,4 vs 10,9 m, p=0,0351), for single site PD (12,9 vs 10,7 m, p=0,0349), non-liver single site PD (15,6 vs 8,1 m, p=0,0066), no liver PD (13,6 vs 10 m, p=0,0043). Median PFS was 4.2 m (95%CI 3,43-43,03). PFS was longer in G2 mCRC (4,5 m vs 2,2 G1 vs 3,3 G3, p<0,0001), in absence of AE over the first 4 cycles (6,53 vs 3,9 m, p=0,0047), cycle 1 (6,1 vs 3,8 m, p=0,0056) and 2 (6,1 vs 3,9 m, p=0,0244) and of dose/schedule changes globally during the first 4 cycles (11,3 vs 3,4 m, p=0,0020), cycle 2 (4,5 vs 3,7 m, p=0,0298), 3 (6,5 vs 3,3 m, p=0,0008) and 4 (6,5 vs 4,2 m, p=0,0080). PFS was improved for single site PD (4,5 vs 3,7 m, p=0,0138), non-liver single site PD (6,5 vs 3 m, p=0,0090), no lung (4,8 vs 3,9 m, p=0,0338) and no liver PD (6,3 vs 3,3 m, p<0,0001). In our study G2 mCRC, low LDH, single site PD, absence of AE, treatment changes and of liver/lung PD were associated with better outcome in pre-treated long term mCRC survivors receiving R.