Abstract 39P
Background
The three active agents (oxaliplatin, irinotecan and 5-FU/leucovorin) have demonstrated synergistic antitumor effects and could probably overcome resistance to doublet combination (FOLFOX/FOLFIRI) for mCRC. Preclinical studies have demonstrated that surufatinib (S, a small-molecule kinase inhibitor of VEGFR1-3, FGFR, and CSF-1R) plus chemotherapy have enhanced antitumor effects by regulating tumor microenvironment. This study aimed to evaluate the efficacy and safety of S plus chemotherapy, explore the difference between doublet vs triplet chemotherapy plus S for mCRC.
Methods
This open-label, 2-arm, phase II trial enrolled pts with mCRC who have progressed after standard first-line doublet chemotherapy. Pts are randomly allocated (1:1) to receive S (250 mg, once daily) in combination with mFOLFOX6/FOLFIRI (depending on first-line) in arm A, or with FOLFOXIRI in arm B, every 2 weeks until disease progression or unacceptable toxicity. Primary endpoint is ORR. Secondary endpoints include PFS, DCR, OS and safety. Simon 2-stage design is used. Each arm plans to enroll 28 pts in stage 1&2. If ≥7/28 pts experienced ≥PR, this arm is worth further investigation.
Results
As data cutoff of 31st Mar 2024, two arms have finished the enrollment (29 pts with 27 evaluable for efficacy and in arm A, 27 pts with 23 evaluable for efficacy in arm B).Median age was 63/60 years, 67/80% were male, 40/47% were ECOG PS 1 and 73/60% had ≥ 2 metastatic sites. The ORR was 25.93% (7/27; 1 CR and 6 PR) in arm A and 34.78% (8/23; 8 PR) in arm B, with DCRs of 81.5% and 82.6%, respectively. Median PFS was 5.52 months (95%CI 3.49-7.55) in arm A and 5.95 months (95%CI 5.63-6.27) in arm B. The most common TEAEs (Total; Grade ≥3) in arm A were anemia (55.17%; 0), neutropenia (44.83%; 13.79%), and leukopenia (41.38%; 3.4%); in arm B were leukopenia (66.67%; 22.22%), anemia (62.96%; 14.81%), and (62.96%; 40.74%).
Conclusions
Surufatinib plus either mFOLFOX6/FOLFIRI or FOLFOXIRI as second-line treatment in patients with mCRC reached its primary end point with acceptable safety profile. The promising results warrant further investigations in a large mCRC cohort.
Clinical trial identification
NCT04734249.
Legal entity responsible for the study
Fujian Cancer Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.