Stoll, Amy C.

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.

341 Background: Genomes of metastatic pancreatic cancers frequently contain intrachromosomal aberrations indicating DNA repair abnormalities associated with sensitivity to DNA damaging agents such as the platinums. Cisplatin was added to a nab-paclitaxel + gemcitabine regimen, which has been determined to improve survival over gemcitabine alone (NEJM 2013; 369:1691-1703). The objectives are to determine the efficacy and safety of nab-paclitaxel and gemcitabine plus cisplatin in patients with Stage IV pancreatic cancer. Methods: Eligibility criteria included Stage IV adenocarcinoma of the pancreas, no prior chemotherapy for systemic disease, KPS ≥ 70; life expectancy ≥ 12 weeks and measurable disease. Doses are nab-paclitaxel 125 mg/m2 undiluted, gemcitabine 1000 mg/m2 in 500 ml of normal saline (NS), each infused over 30 minutes on days 1 and 8 of a 21 day cycle, along with 3 different dose levels of cisplatin (25, 37.5 or 50 mg/m2) in 500 ml of NS infused over 60 minutes, after the nab-paclitaxel infusion. Pre and post cisplatin hydration was given. The maximum tolerated dose and phase II dose of cisplatin is 25 mg/m2. Results: 25 pts were treated; 24 were evaluable (baseline and ≥ 1 follow up CT scan). The most common drug related grade (gr) 3 - 4 adverse events (AEs), n = 25, were thrombocytopenia 76% (gr 3 = 36%, gr 4 = 40%) with no serious bleeding events, anemia 32% (gr 3 = 32%, gr 4 = 0%), neutropenia 24% (gr 3 = 20%, gr 4 = 4%), infection 20% (gr 3 = 16%, gr 4 = 4%), and diarrhea 16% (gr 3 = 16%, gr 4 = 0%). Peripheral neuropathy ≥ gr 3 was seen in only 1 pt (gr 3 = 4%). Grade 5 AEs were infection (1), cardiac arrest (1), and stroke (1). Median time on therapy was 5.5 months, range (1 – 9.5). By RECIST 1.1 criteria, 2 pts had complete response (8.3%), 15 partial response (62.5%), 4 stable disease (16.7%), and 3 progressive disease (12.5%). Median overall survival to date as of 11/10/16 is 16.5 months. Conclusions: Although a small study, the high response rate and landmark evolving median survival are very encouraging. This regimen is being expanded in patients with stage IV pancreatic cancer, neoadjuvant and adjuvant settings. Clinical trial information: NCT01893801.