KEY TAKEAWAYS
- The Phase II trial aimed to evaluate the efficacy of Surufatinib + PD-1 inhibitors in pts with refractory mCRC.
- The primary endpoint was to assess PFS.
- Results revealed that surufatinib with PD-1 inhibitors showed promising survival benefits and manageable toxicity.
Patients (pts) with refractory metastatic colorectal cancer (mCRC) face fewer options post-failure of angiogenic tyrosine kinase inhibitors (TKIs) like fruquintinib or regorafenib. Surufatinib (S, a small-molecule inhibitor of VEGFR 1-3, FGFR1, and CSF-1R) has shown synergistic anti-tumor effects in solid tumors with toripalimab, a PD-1 inhibitor.
Huiting Xu and colleagues aimed to assess the efficacy and safety of combining S with PD-1 inhibitors in pts with refractory mCRC who have progressed on anti-angiogenic TKIs.
Researchers analyzed pts between the age of 18-80 years, with ECOG performance status (0-2), who had progressed after at least two prior treatment regimens (including anti-angiogenic TKIs). Eligible pts were treated with S (250 mg, QD, PO, Q3W) plus PD-1 inhibitors (Q3W) until disease progression, intolerable side effects, or death.
The primary endpoint was to assess progression-free survival (PFS), with secondary goals such as disease control rate (DCR), overall response rate (ORR), overall survival (OS), and safety evaluations.
The results showed that 16 pts (37.5% male) were enrolled until February 29, 2024. Patients had a median age of 56 (37-77), and 81.25% had undergone at least 3 prior therapy lines. Most pts (93.75%) had microsatellite stability, while 56.25% had RAS/BRAF mutations. Of the initial 16, only 13 pts were evaluated for efficacy.
Prior treatments included fruquintinib (median PFS [mPFS] 2.8 months [m] for 9 pts) and regorafenib (mPFS 1.23 m for 4 pts). The median PFS for S+PD-1 inhibitors was 5.22 m (95% CI, 4.40-NA). Overall, total mPFS for fruquintinib/regorafenib sequential S+PD-1 was 9.4 months (95% CI, 4.2-NA), and for pts with at least 3 prior lines of therapy had a mPFS of 6.90 months (95% CI, 4.40-NA) on this combination.
The ORR was 15.38% (2/13), and the DCR was 76.92% (10/13). Grade 3 treatment-related adverse events were experienced by 53.84% of pts, including 2 hyperbilirubinemia, 2 AST and 1 ALT increases, 2 anemia, 1 platelet count decrease, and 1 hypertension. No deaths related to treatment were reported.
The study concluded that S+PD-1 inhibitors demonstrated promising survival benefits and effective anti-tumor activity with manageable toxicity in late-line treatment of refractory mCRC, especially in pts with 3 or more prior therapies. Sequential use of angiogenic TKIs with PD-1 inhibitors may offer clinical potential. Further investigation in larger cohorts is warranted.
The trial was sponsored by Hubei Cancer Hospita.l
Clinical trial: https://www.clinicaltrials.gov/study/NCT05372198
Xu H, Chen R, Yang D et al. (2024). “Surufatinib combined with PD-1 inhibitors as a late-line therapy in patients with refractory metastatic colorectal cancer (mCRC).” Presented at ESMO GI 2024. (Abstract 40P)
