A prospective, single-arm, phase II study of surufatinib in combination with gemcitabine and nab-paclitaxel for the neoadjuvant treatment of resectable and borderline resectable pancreatic cancer.

Abstract

e16442 Background: Nab-paclitaxel combined with gemcitabine (AG) is the standard neoadjuvant treatment regimen for pancreatic cancer (PC). Research shows that gemcitabine can elevate tumor CSF-1 levels and increase M2-TAMs infiltration. Surufatinib (SUR), a multi-targeted tyrosine kinase inhibitor, targeting VEGFR-1/2/3, FGFR-1, and CSF-1R, offers dual anti-tumor effects through anti-angiogenesis and modulating the immune microenvironment. This study aims to explore the efficacy and safety of SUR plus AG as neoadjuvant treatment for high-risk resectable (HR-RPC) or borderline resectable PC (BRPC). Methods: Enrolled patients (pts) had histologically confirmed HR-RPC or BRPC (risk assessed by the Tianjin socring and grading, which evaluates resectability criteria, lymph node metastasis, CA19-9 levels, and prognostic nutritional scores.) and no prior systemic therapy or local radiotherapy. Pts received SUR (250 mg, PO, QD), nab-paclitaxel (125 mg/m², IV , d1, 8, and 15, Q4W), and gemcitabine (1000 mg/m², IV, d1, 8, and 15, Q4W) for 2-6 cycles. The regimen was designed to maximize anti-tumor efficacy while minimizing toxicity through a carefully structured cycle schedule. Pts underwent surgery if R0/R1 resection was accessible. The primary endpoint was the R0 resection rate. Secondary endpoints included the surgical resection rate, downstaging rate, pCR rate, ORR, DCR, and safety. Results: As of Jan 6, 2025, 23 pts completed preoperative treatment and tumor assessment. Median age was 66 years (range: 48-76), with 65.2% female, and 78.3% with lymph node metastasis. The ORR and DCR were 56.5% and 91.3% with 87.0% achieving tumor regression. 18 pts underwent surgery (77.8% RAMPs+22.2% pancreaticoduodenectomy), with a resection rate of 78.2% (18/23). Among surgical pts, median preoperative treatment cycles was 2 (range:1-6), with an ORR of 66.7% and DCR of 100%. The R0/1 resection rate was 88.9%/11.1%, respectively. Pathologic tumor regression was 5.6% complete response, 77.8% moderate/minimal response by CAP criteria. CA19-9 levels decreased by 89.6% (from 378.3 U/ml to 39.3 U/ml) after neoadjuvant therapy. Tianjin scores shifted from 5 to 3, with risks moving from very high/high (11.1%/88.9%) to high/medium (11.1%/88.9%). Downstaging was notable, with cT1/2 increasing from 11.1% to 33.3% in ypT1/2. Treatment-related adverse events included myelosuppression (43.5%), hypertension (30.4%), liver dysfunction (26.1%), hypoalbuminemia (17.4%), and rash (13.0%). Conclusions: Surufatinib in combination with nab-paclitaxel and gemcitabine demonstrated promising efficacy and manageable safety as neoadjuvant treatment for pancreatic cancer. The regimen achieved tumor shrinkage, reduced surgical risk and CA19-9 levels, and resulted in effective downstaging and an excellent R0 resection rate. Clinical trial information: NCT05908747 .