431P Neoadjuvant treatment with regorafenib and capecitabine combined with radiotherapy in locally advanced rectal cancer: A multicenter phase Ib trial (RECAP) SAKK 41/16

Currently high risk locally advanced rectal cancer (LARC) patients (pts) are treated with intensified neoadjuvant chemotherapy and radiation (TNT). The previous study SAKK 41/08 showed that adding Sorafenib to long course chemoradiation (LcCRT) is highly active. This potential improvement in clinical outcome by a multi-TKI as Regorafenib (R) LcCRT was investigated the 41/16 trial. Pts T3-4 and/or N+ M0 were included. Neoadjuvant LcRCT given Capecitabine 825mg/m2d1-d38 28 fractions of 1.8Gy (50.4Gy). R added d1-14 d22-35. phase I part done 3+3 dose escalation (DE) scheme for R. recommended (RD) used cohort expansion (CE). primary endpoints included limiting toxicity (DLT) pathological response (defined near complete regression [npCR] or [pCR] according Dworak) CE. 19 pts required based on one-sided type error 20% power 80% assuming npCR/pCR rate ≥ 40% H1 compared ≤ H0.. 25 Two DLT occurred 120mg, ending RD 80mg daily. RD, 8 (42.1%; CI (lower bound): 30.7%; 95% CI: 20.3%-66.5%) reached endpoint (5 [26.3%] had npCR 3 [15.8%] pCR). One additional patient received no surgery due CR. Downstaging T N seen 15 18 operated (83.3%). All R0 resection clear circumferential margin. Postoperative complications 6 (35.3%), one anastomotic leak grade G4, local infections. most common treatment related adverse events G3 CE diarrhea 2 each. Adding 80 mg LARC both activity. regimen did not prolong time contrast TNT. Toxicity manageable, postoperative expected. deserves further investigation especially efficacy comparision TNT regimens.