Gemcitabine (G) and nab-paclitaxel (nab-P) in patients with refractory advanced pancreatic cancer (PC).

373 Background: There is no standard chemotherapy regimen for PC patients who have progressed on G and fluoropyrimidine-based therapy. Single agent nab-P had limited activity on a second-line phase II trial in PC. Synergistic preclinical studies with G and taxanes have been reported. Nab-P targets stromal cells and leads to improved delivery of chemotherapy to PC cells. The combination of G + nab-P might be an effective approach in pretreated PC. Methods: A retrospective analysis of advanced refractory PC patients treated from Sep 2010 to Aug 2011 with the combination of G + nab-P was performed at the Sylvester Comprehensive Cancer Center. Patients received G 1000mg/m2 and nab-P 100mg/m2 on D1, 8 and 15 of a 28 day cycle. Treatment response was assessed by review of imaging studies using the RECIST criteria, CA19-9 response and symptomatic improvement. The progression-free survival (PFS) and overall survival (OS) were calculated from time of commencement of G + nab-P until documented progression or death respectively. Results: 10 patients were treated with G + nab-P; 60%, 30% and 10% of patients had received 3, 2 and 1 prior chemotherapy regimen. 90% and 80% received prior G or fluoropyrimidine-based regimen respectively. Therapy was discontinued in one patient following only one dose of G + nab-P (Cycle 1, day 1) due to grade 2 thrombocytopenia. The remaining 9 patients received a median of 4 cycles. Two (22.2%) patients had confirmed PR, 3(33.3%) patients had confirmed stable disease while 4 (44.4%) patients progressed on therapy. The median PFS was 13.7 weeks. The median PFS was 20 weeks in patients with PR or SD and 9.9 weeks in patients with PD. Recurrent malignant ascitis resolved in a patient with peritoneal carcinomatosis. Treatment was well tolerated; grade 3-4 hematologic toxicity included anemia, thrombocytopenia and neutropenia in 2, 1 and 2 patients respectively. 70% of patients required G-CSF support. Non hematologic Grade 3-4 toxicities included fatigue, peripheral neuropathy; nausea and vomiting in 3, 2 and 1 patient respectively. Conclusions: G + nab-P resulted in clinical benefit in half of this group of advanced PC patients who had previously progressed on G and fluoropyrimidine-based regimens

Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer

413 Background: The combination of nab-P and Gem improves survival compared to Gem alone in first-line therapy of metastatic pancreatic cancer. Efficacy data with this doublet in previously treated pts are scant. Our group presented preliminary results on 10 pts treated with this two-drug combination in the second and third line setting and herein present updated data on 59 pts. Methods: This IRB approved analysis identified all pts diagnosed with advanced refractory pancreatic cancer, treated with second-line Gem and nab-P at University of Miami and Sylvester Comprehensive Cancer Center between September 2010 and June 2014. Response by RECIST, CA19-9, and symptomatic improvement were assessed. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of Gem + nab-P and were analyzed using the Kaplan-Meier method. Clinical benefit was defined as the percentage of patients with a partial response (PR) or stable disease (SD). Results: Data from59 pts were analyzed. The median age was 60; 55% were male; 54% received Gem + nab-P as second line therapy and 46% received it as third-line or beyond. Five (10%) pts had confirmed PR, 23 (47%) SD and 21 (43%) progressed. Among the 31 (52%) pts who received prior Gem, 18 (58%) had clinical benefit, 3 PR and 15 SD. The median OS was 3.9 months. The median PFS was 3 months. Toxicity appears similar to what has been reported on the MPACT trial with the combination. Conclusions: The clinical benefit seen withGem and nab-P in this group of pretreated pancreatic cancer pts suggests that it can be considered as an option. Additionally, prior Gem treatment appears not to decrease Gem and nab-P benefit in this population. Since nab-P monotherapy has modest activity in pre-treated pancreatic cancer pts, our data suggests a positive interaction between Gem and nab-P that may overcome resistance to Gem. [Table: see text

The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx

460 Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining >25% CDX2 = I, >25% MUC5 = Ga, >25% CDX2 and MUC5 = I/G, >25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for the other histologic subtypes, response to F or G was only analyzed in the 35 metastatic pts with the Ga subtype. 14 were metastatic at diagnosis. 24 males. Median age 57. 21 Hispanic, 14 Non-Hisp. The PFS for Ga treated with F based tx (>12 m) versus G (~9 m) based tx in the 1st line approached statistical significance (p=0.050). In multivariable analysis with adjustments for clinical stage, ECOG, age at dx, there was a significant lower risk of progression in pts treated with F based tx versus G based tx (HR=0.278, p=0.0315). Conclusions: There was near statistical significance favoring F based tx over G based tx in PDAC Ga subtype (p=0.05). Historically, G has proven superior to F as a single agent but our findings suggest F in combination may be superior to G in combination, at least for the treatment of Ga subtype

Percutaneous irreversible electroporation (IRE) in the treatment of hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC) to the liver: A retrospective analysis of the University of Miami experience

272 Background: Percutaneous ablation and transarterial chemo- or radioembolization are commonly used in the treatment of HCC and mCRC to the liver. IRE using the Nanoknif is more versatile than other ablative modalities (such as RFA) in that tumors abutting vascular structures can be treated with IRE without compromise of the vessels or concern for the heat sink effect of nearby blood flow. Methods: We examined the records of patients (pts) referred for IRE for HCC and mCRC. The procedures were all done percutaneously under general anesthesia using a standard protocol. The primary endpoint was progression-free survival (PFS). Responses were assessed using the modified RECIST criteria. Results: Between 1/2010 and 8/2011, 49 pts underwent percutaneous ablation of unresectable HCC and mCRC liver tumors using IRE – 33 with HCC and 16 with mCRC. A total of 76 lesions were treated in 62 sessions; the median number of lesions treated per patient was 1 (range 1-4) and the median tumor size treated was 2.1cm (range 0.8-6). After IRE, 20 pts (41%) had a complete response (CR), 19 (39%) had a partial response and 10 (20%) had stable disease as their best response. The Kaplan-Meier estimated median PFS was 11.3 months (95% CI 9.6-12.9) for all pts, 11.6 months (95% CI 10.2-12.9) for HCC pts, and 10.4 months (95% CI 5.4-15.4) for mCRC patients. The one-year PFS was significantly higher for pts achieving a CR compared to those who did not achieve a CR (75% versus 59%, log rank p = 0.05). The number of liver lesions at baseline and size of the treated lesions were not associated with any differences in survival. The IRE was complicated in 6 pts (12%) by pneumothorax (2), pleural effusion (2), and atrial flutter/fibrillation during anesthesia (2). All pts recovered fully from these complications. One pt died within 1 month of the IRE due to disease progression. Conclusions: IRE of liver tumors is safe. The PFS rates for pretreated mCRC and unresectable HCC are promising. A complete lack of enhancement of the treated lesion on the post-IRE CT scan appears to be associated with longer survival

Cholangiocarcinoma: A joint cancer database analysis.

268 Background: Cholangiocarcinoma is an uncommon malignancy. In addition, only 10-30% of patients are eligible for curative surgical resection due to advanced disease at diagnosis. The role of adjuvant therapy is not yet established. The objective of this analysis is to assess the outcome of patients with cholangiocarcinoma managed with surgery, chemotherapy, radiation, and/or chemo-radiation. Methods: From 1997 to 2007, patients with biliary cancer from the joint tumor registry database at UMH, SCCC, and JHS had their demographics, stage, pathology, treatment (surgical management, adjuvant and palliative therapy) and survival collected. A total of 800 patients with the diagnoses of biliary cancer were reviewed. The site of cancer was the bile duct in 351 patients, gallbladder in 173, and ampulla of vater in 239 patients. Results: Cholangiocarcinoma - adenocarcinoma of the bile duct – in 334 patients of the 351 with bile duct tumors were analyzed. The mean age at diagnosis was 65 (range 26-92) and 55% of patients were male. Stage at presentation was as follows: 22% of patients presented with stage I, 18% with stage II, 21% with stage III, 26% with stage IV, and 13% were unknown. Potentially curative surgical resection was performed in 45% of the patients. 24% received chemotherapy, 20% received radiation, and 14% received chemo-radiation in combination. The overall median survival (MS) of all patients was 13 months - 22, 16, 14, and 10 months for stages I, II, III, and IV respectively. Surgery provided an overall survival benefit for all stages (24 vs. 9 months, p<.001), including stage III (n=31/71; 20 vs. 10 months, p=.026) and stage IV (n=28/88; 23 vs. 6 months, p<.001). Chemotherapy offered a trend to survival benefit for patients with stage IV (13 vs. 6 months, p=.06) and combined stages III and IV (13 vs. 10 months, p=.07). Combination chemo-radiation had a significant survival benefit in stage IV (19 vs. 6 months, p=.022) and in combined stages III and IV (14 vs. 10 months, p=.026). Conclusions: Chemotherapy and chemo-radiation had a positive impact on survival in patients with late stage cholangiocarcinoma. Surgery improved survival in both early and advanced stages. The lack of data on performance status and organ function did not allow factoring these variables in the analysis