Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study (UNION TNT).

Abstract

192 Background: We have demonstrated that neoadjuvant SCRT followed by PD-1 inhibitor plus CAPOX for LARC patients (pts) showed a higher pCR rate and a well-tolerated safety profile in phase III UNION study. Fruquintinib is a potent and highly selective VEGFR inhibitor, which had been approved for previously treated mCRC pts. This study aimed to investigate the efficacy and safety of SCRT followed by fruquintinib plus adebrelimab and CAPOX as a total neoadjuvant therapy for high-risk LARC pts. Methods: In this prospective, open-label, multi-centers, single-arm phase 2 study (NCT06234007), pts diagnosed with newly diagnosed and high risk LARC were recruited. Pts received SCRT (25Gy/5f) followed by six cycles of fruquintinib (4mg, qd, po, q3w,for the initial 6 pts in the safety run-in period, dosage would be adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Primary endpoint was CR rate (including clinical CR & pathologic CR). Secondary endpoints included 3-year EFS rate, OS, R0 resection rate and safety. Results: As of 30 Aug 2024, 45 pts were enrolled (median age 59 years [range: 24-75], 26 males, 23 clinical T4 stage and 20 clinical N2 stage, 36 with EMVI positive, 31 with MRF positive, 22 tumor located ≤5cm from the anal verge). Up to 20 Sep 2024, all pts completed SCRT, 73.33% (33/45), 57.78% (26/45) and 31.11% (14/45) pts completed two, four and six cycles of combination therapy, respectively. At data cut-off, of 33 pts included in the efficacy analysis, 28 pts underwent MRI examination and mrTRG results were available, the remaining 5 pts had early surgery due to AEs/serious AEs. 35.7% (10/28) and 46.43% (13/28) pts were classified as mrTRG1 and mrTRG2, respectively. Of 19 pts who underwent surgery, R0 rate was achieved in all 19 pts (100%) and pCR was achieved in 12 pts (63.16%). Moreover, 1 pt achieved cCR during neoadjuvant therapy, thus the treatment strategy provided a CR rate of 65% (1 cCR plus 12 pCR divided by 20). Grade 3/4 adverse effects (AEs) occurred in 16 pts (47.06%), and most commonly were lymphocyte count decreased (n=6, 18.18%), diarrhea (n=5, 15.15%) and AST increased (n=2, 6.06%). 4 serious AEs reported with intestinal perforation and all achieved pCR after surgery therapy. No treatment related death was reported. Conclusions: SCRT followed by fruquintinib combined with adebrelimab and CAPOX as a total neoadjuvant therapy showed promising CR rate and favorable pCR for high-risk LARC pts, and the safety profile was generally manageable. This treatment strategy might be a potential option as neoadjuvant therapy for high-risk LARC pts. Updated data will be presented in the future. Clinical trial information: NCT06234007 .