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62 Background: Novel hormonal agents (NHAs) such abiraterone (ABI) and enzalutamide (ENZA) have demonstrated similar survival benefits against placebo groups in their respective clinical trials leading to their regulatory approval in both the pre- and post-chemotherapy settings in metastatic castration-resistant prostate cancer (mCRPC). Despite the overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZA in patients with mCRPC in the real-world. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. Patients were selected on the basis of having received androgen deprivation therapy prior to initiating a novel hormonal agent (ABI or ENZA) between 2012 and 2016. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary disease, cerebrovascular disease, heart failure, arrhythmia and other cardiovascular causes). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline confounders including pre-existing cardiovascular disease. Results: The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZA group. Before IPTW, mean age of the ENZA group was higher than the ABI group (78 vs 76). There were more ENZA patients with pre-existing arrythmia (ABI: 10.7%, ENZA: 15.1%) and diabetes (ABI: 21.5%, ENZA: 25.1%). Crude incidence rates of cardiovascular-related hospitalization were of 10 events per 100 person-years (PYs) and of 7 events per 100 PYs for the ABI and ENZA groups, respectively. After applying IPTW, all baseline variables were well balanced across both groups with standardized differences < 0.05. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZA group (IPTW-hazard ratio (HR): 1.79, 95% confidence interval (95%CI): 1.04-3.09). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR: 3.02, 95%CI: 1.17-7.78). Conclusions: In our study population, there was a greater risk of cardiovascular-related hospitalizations for ABI users relative to ENZA users, in particular for hospitalization for heart failure. Given the lack of evidence from randomized head-to-head comparisons of both agents, these results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.

40 Background: The approval of novel hormonal agents (NHAs), abiraterone and enzalutamide, have increased the therapeutic arsenal available in metastatic castration-resistant prostate cancer (mCRPC). However, the use of chemotherapy and other antineoplastics at the end of life has been suggested as an indicator of poor quality of care. In this study, we report the use of NHAs at the end of life in men with mCRPC in the province of Quebec, Canada. Methods: Using Quebec public healthcare administrative databases, we identified patients with prostate cancer who used an NHA (abiraterone or enzalutamide) after androgen deprivation therapy and who died between 2012 and 2016. The primary outcome was the use of an NHA in the 30 days before death. Use of an NHA in the 60 and 90 days before dying, and initiation (first prescription) of an NHA in the 30 days before death were evaluated as secondary outcomes. Multivariable analysis of the primary outcome was performed with logistic regression with results reported as odds ratios (OR) with 95% confidence intervals (95%CI). Results: The cohort consists of 1316 patients who used an NHA over the course of their disease and died at a median age of 78 years old, with 292 (22.2%), 464 (35.3%), and 575 (43.7%) having used an NHA in the 30, 60 and 90 days of life, respectively. Use of NHA 30 days before dying decreased over the study period, from 44.8% in 2012 to 17.0% in 2016 (Cochran-Armitage test p-value < 0.001). On multivariable analyses, later years of death remained associated with lower odds of NHA use 30 days before death (OR 0.74, 95%CI 0.66 to 0.81, p < 0.001). Fifty-eight (4.4%) patients initiated a NHA 30 days before dying. Conclusions: Rates of NHA use 30 days before dying were high initially but decreased over the study period. Further assessment of NHA use at the end of life is warranted to examine if the trend will be maintained given the recent approval of additional oral NHAs for prostate cancer.

38 Background: Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) treatment, however several side-effects are associated with its long-term use. Notably, loss of bone mineral density (BMD) is accelerated which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to properly assess baseline fracture risk. The objective was to examine the proportion of BMD testing in men initiating long-term ADT in Quebec. Methods: The cohort consists of men extracted from Quebec public healthcare insurance administrative databases who were diagnosed with PCa from 2001-2012 and treated by ADT for at least one continuous year. The primary study outcome was the receipt of baseline BMD testing (defined as a BMD test identified in the period from 6 months prior to and up to 12 months after ADT initiation). Multivariable generalized linear mixed with a logit link was performed to identify variables associated with baseline BMD testing accounting for physician clustering. Results: We identified 7,069 patients, of which 887 (12.6%) underwent baseline BMD testing. Baseline BMD testing varied by year of ADT initiation, from 7.7% in 2001-2003 to 12.3% in 2013-2012. Following multivariable analyses, later years of ADT initiation (2004-2006, 2007-2009, 2010-2012, 2013-2015) remained associated with higher odds of baseline BMD testing compared to the earlier years (2001-2003) (ORs ranging from 1.43-1.88; p < 0.001). Conversely, age > 80 (OR 0.73; 95% CI 0.57-0.94; p = 0.001), greater Charlson comorbidity score (OR 0.51; 95%CI 0.34-0.75; p = 0.001), and rural residence (OR 0.60; 95%CI 0.48-0.75; p < 0.001) were associated with lower odds of baseline BMD testing. Conclusions: In our study population, rates of baseline BMD testing in men initiating ADT are low, although the rates increased over the course of the study period. Potential gaps identified in baseline BMD testing include older, more comorbid patients, and rural residence. Additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

180 Background: Esophago-gastric cancers are aggressive malignancies requiring numerous investigations to plan complex multi-modal therapy. The path from initial diagnosis to treatment can be associated with a long delay. This delay and complex patient trajectory may impact quality of life. Given the poor prognosis and highly symptomatic nature of upper GI cancer, a clear and timely access to treatment of crucial importance. We sought to determine the impact of a newly implemented streamlined and structure interdisciplinary pathway for newly diagnosed esophageal and gastric cancer on access times to treatment and quality of life (QoL). Methods: A streamlined pathway for patients referred to a high volume Upper GI Cancer clinic was generated with input from physicians, nutritionists, specialized nurses, and social workers. New diagnosis of esophageal or gastric cancer from 2014-16 were enrolled in this program and consenting patients completed serial QoL questionnaires (ESAS) at baseline, pre-treatment, 1 month post treatment. Dysphagia (DS) was quantified on a 5 point scale. Time intervals (days) were evaluated at various points between diagnosis and start of treatment (diagnosis, CT imaging, first visit with upper GI program, start of treatment). Data presented as median(IQR), * p < 0.05. Results: Of the 251 patients with Upper GI cancer, 153 (61%) consented to participate including 140 esophageal/EGJ and 13 gastric cancer patients. Clinical stage distribution was 17.9% I, 30.7% II, 42.6% III, 8.7% IV. Of the 82 Esoph/EGJ patients with completed QoL questionnaires, 15 (18.3%) patients had severe dysphagia (DS = 3-4) and were prioritized for treatment. Patients with severe dysphagia had reduced time from index endoscopy to treatment (29 (16.3-39.3) vs 43 (32.8-68.0)days)* and first Upper GI clinic to treatment (15 (8.0-23.0) vs 25 (21.0-36.0)*. ESAS surveys showed increased QoL for both patients with and without dysphagia from baseline to pre-treatment indicating that simply entry into the streamlined program improved QoL. Conclusions: Structured interdisciplinary investigative and treatment programs for upper GI cancers can expedite time to treatment and improve QoL.

e16078 Background: Recent analysis using CKCis showed that mRCC patients receiving first-line sunitinib (S) had better survival than patients receiving pazopanib (P) and greater than expected survival for a real world sampling. We conducted further analyses to see if an individualized approach (treatment starting at standard dose/schedule with subsequent schedule/dose alterations based on toxicity) using S results in better outcomes in mRCC patients. Methods: Patients within CKCis diagnosed with clear cell mRCC treated with first-line S or P between January 2011 through December 2015 were analyzed by three treatment groups: 1) S as per individualized approach (SI) 2) S as per product monograph (SS) 3) P as per product monograph (PS). Overall survival (OS) and time-to-treatment failure (TTF) were calculated. Cox regression analysis allowed for adjustment of International Metastatic RCC Database Consortium (IMDC) criteria with age as a continuous variable. Results: A total of 598 patients were identified, 351 patients in SI, 151 patients in SS, and 92 patients in PS. Baseline characteristics are noted in Table 1. Median OS was improved in SI vs SS (37.9 vs 22.3 months (m), p

468 Background: Recent analysis using CKCis, a prospective database, showed that mRCC patients receiving first-line sunitinib (S) had better survival than patients receiving pazopanib (P) and greater than expected absolute survival in the real world setting. We conducted further analyses to see if an individualized approach (treatment starting at standard dose/schedule with subsequent schedule/dose alterations based on toxicity) using S results in better outcomes in mRCC patients. Methods: Patients within CKCis diagnosed with clear cell mRCC treated with first-line S or P between January 2011 to December 2015 were analyzed by three treatment groups: 1) S as per individualized approach (SI), 2) S as per product monograph (SS), or 3) P as per product monograph (PS). Overall survival (OS) and time-to-treatment failure (TTF) were calculated. Cox regression analysis allowed for adjustment of International Metastatic RCC Database Consortium (IMDC) criteria with age as a continuous variable. Results: A total of 573 patients were identified, 261 patients in SI, 201 patients in SS, and 111 patients in PS. Differences in baseline characteristics were noted (Table). Median OS was improved in SI vs. SS (40.8 vs. 22.6 months (m), p

134 Background: A better understanding of taxane sensitivity/resistance in mCRPC is needed to optimize treatment. Preclinically, taxane efficacy has been linked to the ability of microtubules (MT) to inhibit AR nuclear trafficking. In this prospective biomarker study, we used circulating tumor cells (CTCs) from patients (pts) in TAXYNERGY to perform real-time analysis of AR nuclear localization (ARNL) and MT stabilization (bundling; MTB) in order to predict taxane sensitivity. Methods: TAXYNERGY (NCT01718353) is a phase 2 trial randomizing chemo-naïve mCRPC pts 2:1 to docetaxel or cabazitaxel, with a switch to the alternative taxane in the absence of a ≥ 30% PSA drop by C4. Here we present the co-primary biomarker endpoints. CTCs at baseline (C1D1) were compared to CTCs after 1 week of taxane treatment (C1D8), and were analyzed by multiplex confocal microscopy for %ARNL (integrated AR intensity in the cell and nuclear areas) and MTB (assessed for increase compared to C1D1 on a scale from 0–3 from no to most MTB increase). Associations between %ARNL and MTB with clinical outcomes were sought. Results: Of 63 randomized pts, 26 had evaluable CTCs both at C1D1 and C1D8. At C1D8, mean %ARNL was significantly lower in pts achieving a ≥ 50% PSA drop by C4 vs those without (44% vs 64%; p = 0.004). A taxane-induced decrease in mean %ARNL (C1D8 vs C1D1) was associated with a higher rate of ≥ 50% PSA response (73% vs 13%; p = 0.009); mean %ARNL decreased by 18% in responders and increased by 2% in non-responders (p = 0.02). Finally, a taxane-induced increase in mean MTB trended higher in pts achieving a ≥ 30% PSA drop by C4 vs those without (0.69 vs 0.09; p = 0.09); increase in mean MTB score was indicative of response and observed in pts who did not require a taxane switch after C4 (0.75 vs 0.09; p = 0.06). Conclusions: We provide the first prospective data suggesting that taxane-induced shifts in ARNL and MTB (measured in CTCs) may serve as an early biomarker of taxane sensitivity. Consistent with preclinical data, AR nuclear exclusion caused by microtubule bundling may be a clinically-actionable marker of taxane efficacy. Funding: Sanofi Genzyme. Clinical trial information: NCT01718353.

5007Background: TAXYNERGY (NCT01718353), a randomized phase II trial, evaluated early taxane switch with CTC biomarkers to study mechanisms of sensitivity/resistance in men with chemo-naive mCRPC. ...

5031 Background: Microtubule-targeted therapy with taxanes is the only chemo with survival benefit in advanced PC. Emerging molecular evidence suggests sensitivity/resistance to taxanes may relate ...

226 Background: Prostate cancer (PCa) death is mainly due to castration-resistant PCa (CRPC) which results from disease progression despite androgen ablation therapy (ADT). Little is known about clinical outcomes and trends of real-life CRPC management in the present era, which has become very complex. Our study aimed to analyze healthcare services use, clinical outcomes and survival trends in real-life management of CRPC in Quebec, Canada. Methods: The study cohort consisted of 7,123 patients which shown evidence of CRPC from January/2001 to July/2013, selected from the public healthcare insurance programs the Régie de l’Assurance Maladie du Québec (RAMQ) databases. Survival was evaluated by Kaplan-Maier and the difference in survival between pre-/post-docetaxel (Doc) (2002-2005 vs 2008-2011) era by log-rank test. The association between Doc exposure and survival was evaluated by Cox proportional hazards model adjusted for several co-variables. Results: Chemotherapy was offered to 17% of patients, while 45% were kept on maximal androgen blockade (MAB) alone, or offered Abiraterone (3%). Androgen targeted therapies (MAB or Abiraterone) were the treatment of choice for the elderly population (mean age 78.8 and 78 ±7, respectively) while chemotherapy was offered to younger patients (mean age 72 ±7.3). Survival rates at 1 and 2 years after the initiation of chemotherapy were 52% and 26% in post-Doc era vs 46% and 17% in the pre-Doc period. In patients receiving first line chemotherapy only, hospitalization due to PCa was a poor prognostic predictor (HR: 2.0; 95%CI: 1.5-2.6), as expected. In addition among patients without previous hospitalization the risk of death was higher in the pre- vs post-Doc era (HR: 1.7 CI: 1.003-2.851). Conclusions: Patient age seems to be a strong determinant in CRPC therapy selection. In patients without serious complications leading to hospitalization, survival was greatly improved in the post-Doc era. Our data also supports that patients older than those in the TAX327 trial (72 vs 68) may equally benefit from chemotherapy. This is encouraging as we hope to observe comparable results for new approved therapies for CRPC.

424 Background: The proportion and characterization of patients (pts) with metastatic renal cell carcinoma (mRCC) who never start or delay starting targeted therapy (TT) is unknown. It is important to understand and characterize these pts. Methods: Data from the Canadian Kidney Cancer information system (CKCis) database were utilized. CKCis data were collected prospectively from 14 REB-approved academic centers in Canada. The study population included pts with mRCC managed from 2006 (when VEGFR TT became available) to 2014. Results: 920 pts met the inclusion criteria, but 67 pts had

265 Background: Measuring quality of care is required to improve patient outcomes. There are 23 established Quality Indicators in Renal Cell Carcinoma (RCC) (Wood LA et al, JOP 2013) including initiating targeted therapy (TT) at full dose. It is recognized that the dose of TT is important to optimize clinical outcomes. Methods: The Canadian Kidney Cancer Information System (CKCis) is a prospectively maintained database of RCC pts from 14 Canadian academic centers. CKCis data was used to determine the use of TT in metastatic pts, the initial dose in the first line setting, and factors influencing whether pts initiated full dose TT. Descriptive statistics were performed to characterize current practices and a multivariate logistic regression was performed to assess predictors of initiating full dose TT. Results: Between 2006 and 2014, 560 pts received first-line TT and make up the study cohort. 92% received VEGF TT (81% sunitinib; 9% pazopanib; 2% sorafenib) and 8% received mTOR TT (5% everolimus; 3% temsirolimus). All pts receiving mTOR inhibitors received full dose and are excluded from further analysis. Full dose VEGF TT was initiated in 87% on sunitinib, 78% on pazopanib, and 92% on sorafenib. The sunitinib schedule was 4/2 in 81%, 2/1 in 12%, and other in 7%. Pts were less likely to initiate full dose TT if they were older (OR: 1.10, 95% CI 1.06-1.15), female (OR: 2.23, 95% CI 1.09-4.55) or had a worse ECOG PS (2,3,4 vs 0,1) (OR: 2.30, 95% CI 0.95-5.59). Data on initial versus final dose of TT will also be presented. Conclusions: Maximizing exposure to TT is important in metastatic RCC which is why initiating full dose TT was prioritized as a key QI in RCC. In this study, 87% of pts were initiated on full dose VEGF TT in the first line setting, and 100% of pts on mTOR TT which is higher than predicted. Those less likely to start on full dose VEGF TT were older, female and had a lower ECOG PS. The gender discrepancy will be explored in future studies.

e16029 Background: Medical or surgical castration are the treatments of choice for hormone-sensitive prostate cancer with a high-risk of disease recurrence or progression. In addition, androgen abl...

e15044 Background: We have previously identified Docetaxel, Cisplatin, and 5FU (DCF) as a highly effective regimen in the neoadjuvant setting for locally advanced adenocarcinoma (ADC) of the esophagus and esophago-gastric junction (EGJ). However there is ongoing debate whether chemotherapy alone provides adequate local or regional control. We hypothesized that DCF combined with enhanced local surgical control would result in a low rate of local or regional recurrence. Methods: A prospective entered database of all esophageal/EGJ ADC pts resected at a high volume referral center was reviewed for cases treated with neoadjuvant DCF (Docetaxel 75mg/m2, Cisplatin 75mg/m2, 5FU 750mg/m2x120 hrs CIV) Q3weeks x3, followed by en-bloc resection with extended lymphadenectomy (D2). Follow up included physical exam Q3m x 2 yrs then Q6m, and endoscopy and CT chest/abdo/pelvis performed Q6 m. Recurrence was defined as: Local = biopsy on endoscopy; Regional = regional lymph nodes; Distant = distant organ or non-regional lymph nodes. Data presented as Median (Range). Results: Of 281 pts in the database, 89 (75%male, 63yrs(24-80)) underwent pre-op DCF and resection for locally advanced ADC (cT3 93%;cN+ 73%) of the EGJ (51%) or distal esophagus (49%) from 3/07-10/12. After overall follow-up of 37(6-72) months, 37 (42%) have recurred at 15(6-33) months. Sites of recurrence include Distant only in 29/37, Regional only in 5/37, and Regional and Distant in 3/37. First site of distant recurrence was peritoneum (14/37), liver (10/37), non-regional lymph nodes (10), brain/ovary/pleura (2 each), and bone(1). No patient had local recurrence alone. 3/5 patients with regional recurrence underwent salvage chemoradiotherapy and are alive without disease at 36 months (30-47) after recurrence. Conclusions: En-bloc resection with extended lymphadenectomy after DCF for locally advanced ADC of the esophagus and EGJ is associated with a low rate of local and regional recurrence. As vast majority of recurrences are distant, our data supports the notion that efforts to improve outcomes in these pts should concentrate on enhancing systemic, rather than local, therapy.

394 Background: We analyzed renal cell carcinoma (RCC) brain metastasis (BM) risk factors and compared BM occurrence in advanced RCC treated with or without antiangiogenic agents (AAA). Methods: Data from all consecutive metastatic RCC patients (pts) treated in the Northern France Cancer Center (Centre Oscar Lambret, Lille) between 1995 and 2008 were reviewed. Eligible pts had histologically confirmed advanced RCC without synchronous BM at the time of metastasis diagnosis. Bellini duct and neuroendocrine carcinoma and sarcoma were excluded. AAA were sorafenib, sunitinib, bevacizumab, temsirolimus, and everolimus. Characteristics of the two groups, treated with or without AAA, were compared with a Fisher exact test. Impact of AAA on overall survival (OS) and BM-free survival (BMFS) was explored by Kaplan-Meier method and adjusted to confounders parameters in a Cox model. Results: A total of 199 pts with advanced RCC were identified, 51 treated with AAA and 148 treated without AAA. The median follow-up duration was 40 months. BM occurred in 35 pts. As expected in this retrospective analysis, characteristics between AAA treated and non AAA treated groups were unbalanced for 11 parameters including age, Motzer prognostic factors, performance status and favoring better prognostic factors in the AAA treated group. The median overall survival was 24 months. Overall survival was higher in patients with AAA versus patients without AAA (31 versus 18 months, hazard ratio (HR) 0.67 [0.45–0.97], p=0.038). The AAA were not associated with better BMFS (HR=0.58 [0.26–1.30], p=0.187). The alkaline phosphatase was an independent prognostic factor for BM (p=0.05). In multivariate cox model, AAA treatment improved the OS (adjusted HR 0.60 [0.38–0.94] but not the BMFS (adjusted HR 0.53 [0.22–1.32]. Conclusions: In this retrospective single center study, elevated alkaline phosphatase is a predictive factor for brain metastasis in metastatic RCC. AAA significantly improved overall survival in advanced RCC without any significant impact on brain-metastasis-free survival. No significant financial relationships to disclose.