711PPHASE IB TRIAL OF NAB-PACLITAXEL PLUS GEMCITABINE, CAPECITABINE, AND CISPLATIN (PAXG REGIMEN) IN PATIENTS WITH STAGE III PANCREATIC ADENOCARCINOMA

ABSTRACT Aim: Gemcitabine (GEM) and nab-paclitaxel (nab-P) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma (PA). Given the synergism of taxanes with platinum compounds and fluoropyrimidines, we determined the recommended phase 2 dose (RP2D) of nab-P in combination with cisplatin, capecitabine, and GEM (PAXG regimen) in a phase Ib trial in patients (pts) with stage III PA (NCT01730222). Methods: GEM, cisplatin and capecitabine were given at fixed dose (800, 30, and 1250 mg/m2, respectively) q 2 weeks. Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 (level 1), to 125 (level 2) and 150 mg/m2 (level 3) q 2 weeks. The maximum tolerated dose (MTD) was defined as the dose at which > 2 out of 3-6 pts developed dose-limiting toxicity (DLT) during the first month of therapy. DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days; G ≥ 3 febrile neutropenia, fever ≥38.5°C, thrombocytopenia, diarrhea, nausea or vomiting; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks. Results: Between Dec 2012 and Mar 2014, 23 pts (16 males; median age 63 years) with unresectable (according to a surgical team performing >100 duodenocephalopancreasectomy/year) stage III PA, were enrolled at a single institution (3 at level 1, 5 at level 2, 15 at level 3). To date, 197 cycles of PAXG were administered. Therapy is ongoing in 5 pts at level 3. No DLT has occurred. Worse per patient toxicity was G3/4 neutropenia 29/29%; G3 fatigue 14%; G3 neuropathy, anemia, nausea, diarrhea 7%. After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90%. To date, a partial response (PR) was observed in 15 pts (65%) and stable disease (SD) in 8 pts; among 20 pts with positive PET scan a complete response was observed in 8 (40%), PR in 10 (50%), SD in 2; 19 pts had elevated basal CA19-9 which was reduced by >50% in 18 (95%); 15/16 (94%) pts with mature follow-up were progression-free at 6 months from therapy start. Conclusions: The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks. Preliminary results are promising and a phase II randomized trial with this regimen is ongoing. Disclosure: M. Reni: Participation in an Advisory Board : Merck; Celgene; CLOVIS; Genentech; Boehringer L. Gianni: advisory board Celgene. All other authors have declared no conflicts of interest.