Nab-paclitaxel plus S-1 induction chemotherapy for patients with locally advanced pancreatic cancer: A multicenter, open-label phase 2 study.

4225 Background: The prognosis of locally advanced pancreatic cancer is dismal. The objective of the present study was to evaluate safety and efficacy of nab-paclitaxel plus S-1 in previously untreated locally advanced pancreatic cancer. Methods: This multicenter, single-arm phase 2 study was conducted at 4 centers in China. Patients with Eastern Cooperative Oncology Group performance status of 0-1 received up to 8 cycles of nab-paclitaxel 120 mg/m² (day 1,8) plus 80-120mg/d S-1 (day 1-14 each 21-day cycle). After induction, patients without disease progression or unacceptable adverse events were eligible to receive continued therapy according to investigators’ evaluation, including: continued chemotherapy, chemoradiation, or surgery. The primary endpoint was 6-month progress-free survival rate. The secondary endpoints were progress-free survival, overall survival, objective response rate, R0/R1 rate and safety. The reported efficacy outcomes were analyzed in the intention-to-treat population, and safety outcomes were analyzed in the treated population. This trial is registered with ClinicalTrials.gov, NCT03885219. Results: Between April 25, 2019, and March 29, 2023, 60 patients were enrolled in the study. 31 (51.7%) of 60 enrolled patients discontinued induction therapy, with reasons including disease progression (13 21.7% patients), adverse events (12 20.0% patients), alteration in treatment (4 6.7% patients), and withdrawal from study (2 3.3% patients). 29 (48.3%) of 60 enrolled patients completed induction treatment, 22 (36.7%) patients finished all 8 cycles of treatment, and 11 (18.3%) patients underwent surgery (10 achieved R0/R1 resection status). The 6-month progression-free survival rate was 71.0% (95%CI: 57.6%-80.9%); 12-month progression-free survival rate was 45.0% (95%CI: 32.0%-57.2%) and 12-month overall survival could reach up to 83.3% (95%CI: 70.3%-90.9%). The median progression-free survival was 11.1months (95% CI: 8.1-14.2); median overall survival was 20.2 months (95% CI: 11.2-29.2). During induction, 54 patients achieved disease control and the disease control rate was 90.0% (95% CI: 79.5%-96.2%). 16 patients had a best response of partial response; the objective response rate was 26.7% (95% CI: 16.1%-39.7%). Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 32 (53.3%) patients. The most common grade 3 or higher TRAEs were neutropenia (23 38.3% of 60 patients), followed by leukopenia (13 21.7%) and fatigue (4 6.7%). No treatment-related deaths were reported. Conclusions: The data from this trial supports the favorable and efficacy of nab-paclitaxel plus S-1 for locally advanced pancreatic cancer, as well as the possibility of converting unresectable disease into surgically resectable disease. Clinical trial information: NCT03885219 .