Raymond S. McDermott

Response to second-line chemotherapy (Ctx) in advanced urothelial carcinoma: A pooled retrospective analysis of the correlation between objective response rate (ORR) and progression-free survival (PFS) and overall survival (OS).

354 Background: Second-line ctx for advanced urothelial carcinoma (UC) constitutes a substantial unmet need. A commonly used endpoint in phase II studies is ORR, however it is unclear whether this translates to a benefit in OS and PFS. We previously examined pooled OS, PFS, ORR and DCR in second line ctx in advance UC. We now are now determining whether increased ORR correlates with improved PFS and OS. Methods: Published second-line studies were identified from PubMed between 1997- 2012 and were reviewed for data extraction. Pearson correlation coefficient was used to determine correlation between ORR and OS and PFS. Results: 25 prospective studies of second-line ctx for progressive advanced UC were identified (22 non-randomised, 3 randomised) (n= 1,297). The majority of studies (88%) were phase II. 12 studies investigated combination regimens and 13 studies monotherapy. All studies allowed adjuvant and primary chemotherapy as first-line but only 7 studies reported median time from last chemotherapy. The...

Influence of ABO blood group on the natural history of advanced pancreatic adenocarcinoma (PC).

307 Background: An association between blood group (ABO) and PC has been demonstrated at epidemiologic and genomic levels. Variations in ABO type may lead to higher pro-inflammatory cytokines levels with modifications in cellular adhesionand signalling promoting carcinogenesis. This study investigated the influence of ABO on the clinical behaviour of advanced PC in patients (pts) , treated with chemotherapy (ctx). Methods: Pts with confirmed PC were identified from 4 institutional databases. Inclusion criteria were unresectable (UPC) or metastatic disease (MPC), receipt of ctx and availability of ABO data. Clinicopathologic details were collected. 200 random anonymied non-cancer ABO samples were collected as control. Descriptive statistics and survival analyses were performed. Results: Between 2001 and 2012, 222 pts met inclusion criteria. Median age was 63 years (range: 33 – 83) 56% were males. 60% of pts had MPC and 27% received doublet ctx. ABO distribution was: A (40%), AB (5%), B (11%) and O (44%). T...

Identification of distinct phenotypes of locally advanced pancreas cancer.

369 Background: A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease (LAPC). Optimal treatment remains controversial. There is no consensus on timing of chemotherapy and radiotherapy. We sought to analyse the clinical course of LAPC in order to identify potential distinct clinical phenotypes. METHODS Patients (pts) diagnosed with LAPC who survived >2 months were identified from prospectively maintained databases from two medical oncology departments in teaching hospitals. Demographics and clinical details were collected. Sequential restaging scans were reviewed for each pts to identify date and pattern of progression. Time to progression (TTP), time from progression to death (TTD) and overall survival (OS) were defined as time from histologic diagnosis to time of radiographic progression, time from radiographic progression to death and the summation of TTP and TTD, respectively. Survival was estimated with Kaplan-Meier method and compared with log-rank test. RESULTS Between Mar 2005 and Apr 2011, a total of 40 pts were identified. Median age was 66yrs (range: 43 - 74) and 60%(n=24) were males. Median OS for entire cohort was 11.3mos. Of 40 pts, 20(50%) had local only progression (LP) and 16(40%) had metastatic progression (MP) at first documentation of disease progression, while 4 pts (10%) had stable disease (2 died with no evidence of progression and 2 remain on treatment). TTP was 4.0 vs 5.6mos HR 0.97 (95% CI 0.49 - 1.93, p=.94) for LP and MP, respectively. Three of the pts with LP (15%) eventually developed metastatic disease after a median of 4.2 mths (3.7 - 9.6). For MP pts, five had concurrent local progression. Sites of disease were lungs(8), peritoneum(5), liver(3) and bone(1). TTD for LP and MP was 5.6 vs 1.4mos HR 0.62 (95% CI 0.28 - 1.39, p=.24), and OS was 13.2 vs 8.0mos, HR 0.59 (95% CI 0.28 - 1.25, p=.17) respectively. CONCLUSIONS We identified two subgroups of LAPC with clinically distinctive behaviour, one local-dominant progression with low predilection for distant metastases, and another with rapid metastatic development and worse survival. Early recognition of these phenotypes might allow a more tailored treatment approach to improve outcome.