Nab-paclitaxel plus S-1 as first-line treatment in patients with advanced pancreatic adenocarcinoma.

Abstract

e15788 Background: Nab-paclitaxel plus gemcitabine and FOLFIRINOX showed survival advantage comparing to gemcitabine monotherapy in metastatic pancreatic cancer (PAC). However, the objective response rates (ORR) were about 30% and still unmet clinical expectation. S-1 is an oral fluoropyrimidine derivative showed comparable and superior clinical benefit in treatment of unresectable and postoperative PAC comparing to gemcitabine. Since nab-paclitaxel and S-1 provided additional clinical benefits in PAC, we conducted a single-arm, phase II trial to investigate the efficacy and safety of nab-paclitaxel plus S-1 as first-line treatment in patients with locally advanced and metastatic PAC. Methods: Nab-paclitaxel was given at 120 mg/m2 intravenously on day 1 and 8, in combination with S-1 which was orally administered (80-120 mg/d according to the body surface area) on day 1-14 of each 21-day cycle, for 6 cycles. The primary endpoint was ORR, secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: Sixty patients including 5 locally advanced and 55 metastatic PAC received a median of 4 cycles (range from 2 to 6). The ORR by either blinded independent review or investigator assessment was 50.0% (Table). Median PFS and OS were 5.7 months (95%CI, 4.9 to 6.6 m) and 9.3 months (95%CI, 8.3 to 10.3 m), respectively. The most common adverse events were neutropenia, sensory neuropathy, and nausea/vomiting. Grade 3 and 4 neutropenia were 22.3% and 11.7%, grade 3 sensory neuropathy was 5%. The patients with grade 3 and 4 neutropenia, and those with biochemical response (50% reduction of CA19-9) achieved better ORR (75% and 76.7%, respectively). Of 52 patients with elevated CA19-9 at baseline, 32 patients (61.5%) had biochemical response showed a better median OS than those without the biochemical response (15.9 m versus 5.7 m, P=0.029). Conclusions: Nab-paclitaxel plus S-1 showed encouraging ORR and being tolerated. Future phase III randomized clinical trial in advanced PAC is warranted. Clinical trial information: NCT02124317. [Table: see text]