Abstract 40P
Background
Refractory mCRC patients (pts) had limited treatment options after failing with angiogenic tyrosine kinase inhibitors (TKIs, ie, fruquintinib or regorafenib). Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) has shown synergy antitumor activity with toripalimab (a PD-1 inhibitor) in solid tumors. Here, we evaluated the efficacy and safety of S plus PD-1 inhibitors in refractory mCRC pts who failed to anti-angiogenic TKIs.
Methods
This open-label, single-center, phase II study (NCT05372198) recruited mCRC pts aged 18-80 years, ECOG PS 0-2, who progressed after at least two treatment regimens (anti-angiogenic TKIs must be included). Eligible pts received S (250mg, QD, PO, Q3W) plus PD-1 inhibitors (Q3W) until disease progression, intolerable toxicity or death. The primary endpoint was PFS, secondary endpoints included DCR, ORR, OS and safety.
Results
AS of Feb 29 2024, 16 pts (37.5% male, median age 56 years, range 37-77, 81.25% with at least three prior therapy lines, 93.75% with microsatellite stability, and 56.25% with RAS/BRAF mutation) were enrolled. 13 pts were efficacy evaluable. 9 pts had previously received fruquintinib (mPFS 2.8m), 4 regorafenib (mPFS 1.23m). The mPFS for S+PD-1 was 5.22 months (95% CI, 4.40-NA). Total mPFS for fruquintinib/regorafenib sequential S+PD-1 was 9.4 months (95% CI, 4.2-NA). For pts treated with at least 3 prior lines of therapy, the mPFS on S+PD-1 was 6.90 months (95% CI, 4.40-NA). The ORR was 15.38% (2/13), and DCR was 76.92% (10/13). 7 (53.84%) pts experienced grade 3 treatment emergent adverse events, including 2 hyperbilirubinemia, 2 AST increased, 2 anemia, 1 ALT increased, 1 platelet count decreased and 1 hypertension. No treatment related death was reported.
Conclusions
Combination of surufatinib and PD-1 inhibitors showed encouraging survival benefits and promising anti-tumor activity with acceptable toxicity in the late-line treatment of refractory mCRC, especially for patients who received at least 3 lines of previous therapies. In addition, angiogenic TKIs sequential angiogenic TKIs plus PD-1 may have potential clinical values. The results warrant further investigations in a large cohort.
Clinical trial identification
NCT05372198; Release date: May 12, 2022.
Legal entity responsible for the study
Hubei Cancer Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.