Nab-paclitaxel plus S-1 as first-line followed by S-1 maintenance for advanced pancreatic adenocarcinoma: a single-arm phase II trial

Abstract

PurposeWe conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with nab-paclitaxel and S-1 followed by S-1 maintenance therapy.MethodsNab-paclitaxel was administered intravenously on days 1 and 8 at 120 mg/m2. S-1 at 120 mg/day (for surface area ≥ 1.5 m2), 100 mg/day (for surface area between 1.25–1.5 m2), and 80 mg/day (for surface area < 1.25 m2) were given two times daily on days 1–14 every 3 weeks. Patients who achieved response and stable disease after 6 cycles were given S-1 maintenance treatment in the same schedule until disease progression or unacceptable toxicity developed. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Between 01/2015 and 07/2017, 32 patients were enrolled.ResultsThe ORR in the intention-to-treat (ITT) population (N = 32) was 53.1%, and the DCR was 87.5%. In the 30 evaluable patients, the ORR and DCR were 56.7 and 93.3%, respectively. The median follow-up time was 18 (range 12–36) months, the median PFS was 6.2 (range 4.4–8) months, and the median OS was 13.6 (range 8.7–18.5) months. The incidence of grade 3/4 neutropenia was 27.6%. Other grade 3 adverse events included 1 (3.1%) hand–foot syndrome, 1 (3.1%) rash and 2 (6.3%) diarrheas.ConclusionsNab-paclitaxel and S-1 regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer.

A Chinese Retrospective Multicenter Study of First-Line Chemotherapy for Advanced Pancreatic Cancer

“…The mPFS rate was 6.2 months (range 4.4–8), and the mOS rate was 13.6 months (range 8.7–18.5). The incidence of grade 3/4 neutropenia was 27.6% [ 13 ], which was similar to our study. In another single-arm, single-center, phase 2 trial, AS and GS were administered to patients with APC.…”

Gemcitabine plus nab-paclitaxel followed by maintenance treatment with gemcitabine alone as first-line treatment for older adults with locally advanced or metastatic pancreatic cancer

“…Of note, although the above-mentioned retrospective experience confirmed the effectiveness and safety of first-line Gem/NabP in a real world setting, grade 3-4 hematologic toxicity occurred frequently and dose reductions were needed in a higher proportion of patients compared to our report (80% vs. 25%). A recent phase III study analysing NabP plus the oral fluoropyrimidine derivative S-1 followed by S-1 as maintenance treatment for advanced PC patients reported results in terms of ORR (53.1%), median PFS (6.2 months), and OS (13.6 months) similar to our analysis [15]. However, the median age of the study population was much younger (53 vs. 77 years) compared to our report and only 6 patients were over 80 years old.…”

<p>Efficacy and Safety of Nab-Paclitaxel Plus S-1 versus Nab-Paclitaxel Plus Gemcitabine for First-Line Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma</p>

“…Two single-arm phase II trials in China reported by Shi et al and Zhang et al showed promising survival (median OS, 9.4-13.6 months) and high ORR (50.0-53.1%) with first-line nab-P/S in patients with advanced PDAC. 13,14 The remarkable results of ORR also indicated the possible role of nab-P/S in the neoadjuvant setting for LAPC. The triweekly regimen of nab-P/S was used in these two trials.…”

“…11,12 In two phase II studies in China, the new combination of nab-paclitaxel plus S-1 showed a remarkable ORR of 50.0-53.1% with good OS and favorable safety profiles as first-line therapy for advanced PDAC. 13,14 Hence, we conducted this retrospective study to evaluate the efficacy and safety of first-line chemotherapy with nab-P/S versus nab-P/G in patients with advanced PDAC.…”