Nab-Paclitaxel Plus S-1 Shows Promise as Induction Therapy for Locally Advanced Pancreatic Cancer
核心洞察
A multicenter phase II trial found nab-paclitaxel plus S-1 (SnP) achieved a 71.0% 6-month progression-free survival rate as induction therapy for locally advanced pancreatic cancer (搜索) (LAPC).
The regimen demonstrated a median overall survival of 20.2 months and a disease control rate of 90.0%, with 10 of 60 initially unresectable patients achieving R0/R1 resection.
Grade 3 or higher adverse events occurred in 53.3% of patients, with neutropenia (38.3%) as the most common, suggesting favorable tolerability compared with other regimens.
A multicenter, open-label, single-arm phase II trial has demonstrated that nab-paclitaxel plus S-1 (SnP) delivers promising efficacy with acceptable tolerability as induction therapy for patients with locally advanced pancreatic cancer (搜索) (LAPC). The study, conducted across four hospitals in China, represents the first prospective evaluation of SnP specifically in the LAPC setting, addressing a significant evidence gap in a disease where treatment approaches have largely been extrapolated from metastatic pancreatic ductal adenocarcinoma (搜索) (PDAC) data.
Pancreatic cancer carries a 5-year survival rate of only 13%, and radical resection—the only curative approach—is feasible in just 10%–20% of newly diagnosed patients. LAPC, though lacking distant metastasis, typically invades adjacent critical vasculature, rendering tumors unresectable. Because no universally accepted standard first-line regimen for LAPC has been established, the National Comprehensive Cancer Network (NCCN) recommendations for LAPC remain Category 2A rather than Level 1 evidence.
Study Design and Patient Population
The trial enrolled 60 patients between April 25, 2019, and March 29, 2023, from four centers in China. Eligible patients had histologically or cytologically confirmed pancreatic adenocarcinoma classified as LAPC according to NCCN guidelines (Version 1, 2019 criteria), defined as solid tumor contact greater than 180° of the superior mesenteric artery (SMA) or celiac axis (CA) and unreconstructable superior mesenteric vein/portal vein (SMV/PV) or common hepatic artery. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 and measurable lesions per RECIST v1.1.
Patients received induction chemotherapy with nab-paclitaxel administered intravenously at 120 mg/m² over 30 minutes on days 1 and 8 of a 21-day cycle, combined with oral S-1 dosed by body surface area (80–120 mg/d) twice daily on days 1–14. The primary endpoint was the 6-month progression-free survival (PFS) rate, with secondary endpoints including PFS, overall survival (OS), objective response rate (ORR), disease control rate (DCR), R0/R1 resection rate, and safety.
Efficacy Results
At a median follow-up of 15.6 months (range: 1.31–72.1), the trial met its primary endpoint with a 6-month PFS rate of 71.0% (95% CI: 57.6%–80.9%). The median PFS was 11.1 months (95% CI: 8.1–14.2), and the median OS was 20.2 months (95% CI: 11.2–29.2). The 12-month OS rate was 83.3% (95% CI: 70.3%–90.9%), and the 24-month OS rate was 45.7% (95% CI: 31.3%–59.0%).
No patient achieved a complete response, but partial response was observed in 16 patients (26.7%), stable disease in 38 (63.3%), and progressive disease in 5 (8.3%). The ORR was 26.7% (95% CI: 16.1%–39.7%), and the DCR was 90.0% (95% CI: 79.5%–96.2%). Among 46 patients with abnormal baseline CA19-9 levels, 32 (69.6%) achieved a reduction of at least 50%, and 27 (58.7%) achieved a reduction of at least 70%, with CA19-9 levels normalizing in 17 patients (37.0%).
Notably, 11 patients (18.3%) underwent surgery, with 10 (90.9%) achieving radical resection and all of those (90.9%) attaining R0/R1 resection. The authors noted that although all individuals were classified as unresectable at baseline, 10 of 60 achieved R0 or R1 resection following induction, suggesting SnP may convert a subset of initially unresectable tumors to resectable disease.
Safety Profile
In the treated population of 60 patients, 58 (96.7%) experienced treatment-related adverse events (TRAEs) of any grade, with 32 patients (53.3%) experiencing grade 3 or higher TRAEs. The most common grade 3 or higher TRAEs were neutropenia (23 patients, 38.3%), leukopenia (13 patients, 21.7%), and fatigue (4 patients, 6.7%). The most common grade 1–2 TRAEs were anemia (28 patients, 46.7%) and peripheral neuropathy (25 patients, 41.7%). No treatment-related deaths due to toxicity were reported.
The authors highlighted that the 53.3% rate of grade 3 or higher adverse events compares favorably with the LAPACT study, where grade 3 or higher adverse events occurred in 80% of patients receiving gemcitabine plus nab-paclitaxel. Dose reduction occurred in 13 patients (21.7%), a rate lower than that reported for gemcitabine plus nab-paclitaxel, FOLFIRINOX, and NALIRIFOX (搜索).
Clinical Context and Limitations
The study addresses a notable gap in LAPC-specific evidence. While the MPACT trial established gemcitabine plus nab-paclitaxel and the NAPOLI-3 trial demonstrated positive outcomes with NALIRIFOX (搜索) in metastatic disease, few regimens have undergone dedicated prospective analysis in LAPC. The authors noted that in Asian populations, tolerability to FOLFIRINOX may limit its routine use due to treatment-related toxicities and the need for dose modifications.
The researchers cautioned that interpretation of median PFS and OS should be undertaken with care, as only 48.4% of patients (29/60) completed induction therapy, and a substantial proportion subsequently received heterogeneous postinduction treatments. The study's single-arm, non-randomized design, investigator-determined postinduction treatment selection, lack of central imaging review, limited sample size from four Chinese centers, and relatively short median follow-up of 15.6 months were cited as limitations that may reduce the generalizability of findings to non-Asian populations.
The authors concluded that SnP "showed superior efficacy with mild toxicity, which may prolong patient survival," and suggested it "could be an alternative induction therapy option for LAPC, especially in patients who cannot tolerate mFOLFIRINOX and NALIRIFOX (搜索)." They emphasized that these results warrant confirmation in future randomized studies to clarify comparative benefit and optimal sequencing strategy.