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e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.

2057 Background: To date, a comprehensive evaluation of core limitations in clinical trials leading to anti-cancer drug approvals by the US Food and Drug Administration (FDA) has not been undertaken.The aim of this analysis was to assess the percentage of clinical trials with core limitations, defined as lack of randomization, lack of overall survival data, inappropriate use of crossover, and use of sub-optimal control arms that led to FDA approvals from 2014 to 2019. Methods: This observational analysis included all approved anti-cancer drug indications by the FDA from July 2014 through July 2019. All indications were investigated and each clinical trial evaluated for design, enrollment period, primary endpoints, and presence of core limitations. The standard of care therapy was determined by evaluating the literature and published guidelines 1-year prior to start of clinical trial enrollment. Crossover was examined and evaluated for optimal use. We then calculated the percentage of approvals based on clinical trials with any or all core limitations. Results: A total of 187 anti-cancer approvals were evaluated. The number of anti-cancer drug approvals doubled over time with 68 in first half of study period (June 2014 to December 2016) to 119 in second half of study period (January 2017 to July 2019). Of those, 125 (67%) were based on a clinical trial with at least one core limitation. 64 (34%) approvals were based on a single-arm clinical trial. Of the remaining 123 approvals based on randomized trials, 60 (32%) had a core limitation. Of all randomized trials, 37 (30%) lacked overall survival benefit, 31 (25%) had a sub-optimal control, and 17 (14%) used crossover inappropriately. Conclusions: The majority of cancer drugs are approved based on clinical trials with core limitations. Efforts to minimize core limitations at the time of clinical trial design are essential to ensure that new anti-cancer drugs being marketed truly improve patient outcomes over current standards.

e20518 Background: Gut microbiome dysbiosis is correlated with graft-versus-host disease (GVHD) in allogeneic stem cell transplant (allo-SCT) patients. In the allo-SCT population, antibiotics have been associated with increased risk for GVHD mortality and relapse due to loss of gut obligate anaerobes . It has been shown that antibiotics may negatively impact the efficacy of checkpoint inhibitors for patients with solid tumors. Based on these studies, we performed a retrospective analysis to determine if antibiotic treatment affects outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: This is a single institution retrospective study at Hackensack University Medical Center. A list of consecutive MM patients treated from 1/2012 to 12/2015 was obtained and an electronic medical record review of the first 217 who received ASCT was performed. Baseline characteristics, treatment history, transplant course and antibiotic treatment (including β-lactams, fluoroquinolones, macrolides, metronidazole, and vancomycin) were reviewed. Prophylactic antibiotics were excluded. Response was defined using the IMWG criteria. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log rank tests were used to compare the difference in survival between stratified groups. The LASSO cox regression analysis method was used for multivariate analyses of PFS and OS. Results: Of the 217 patients, 205 patients were available for analysis. Median age at ASCT was 61. β-lactams were associated with decreased median PFS (1.95 vs 4.77 years (yrs), p < 0.01) and decreased median OS (7.51 vs 13.45 yrs, p = 0.01). Multivariate analysis adjusting for lasso-selected age, gender, complete remission (CR) after ASCT, and ISS demonstrated independent progression risk associated with β-lactam use (HR = 2.00, 95% CI, 1.28–3.12, p < 0.01). β-lactams were associated with worse OS in multivariate analysis adjusting for lasso-selected age, gender, CR after ASCT and high risk cytogenetics (HR = 1.89, 95% CI, 1.07–3.40, p = 0.03). Conclusions: In this preliminary study, β-lactams predicted for decreased PFS and OS compared to patients who did not receive β-lactams in MM patients undergoing ASCT. The study was limited by its retrospective nature but demonstrates one of the first evaluations of antibiotic effect on the ASCT population in MM. Prospective studies evaluating the impact of antimicrobials on patient outcomes and the gut microbiome are ongoing.

30 Background: BM in patients (pts) with CRPC are associated with shorter overall survival (OS) and higher costs. BRI zoledronic acid and denosumab are frequently used to prevent skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line therapy for men with metastatic CRPC. We aimed to assess the impact of BRI on OS and time to first SRE (ttSRE) of pts receiving 1st line treatment AA for CRPC with BM. Methods: A retrospective cohort of pts starting AA as 1st line therapy for CRPC with BM between 2013-2016 was identified through 8 hospitals’ IRB approved registries. Pts were classified by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. Kaplan-Meier method and Cox models were used to assess OS and ttSRE with hazard ratio (HR) estimates (95% CI). Results: Of the 745 pts included (543 deaths), 529 (71.0%) had AA alone and 216 (29.0%) AA+BRI. Median follow-up was 23.5 months. Pts receiving concomitant BRI showed a significantly longer OS and a 35% reduced risk of death compared to AA alone (HR=0.65; 95% CI, 0.54-0.79; P5, PS 0 vs. ≥1, and PSA are independently associated with longer OS. Conclusions: The addition of BRI to 1st line AA for CRPC men with BM was associated with improved OS, particularly in HV, and worsened ttSRE, more evident in LV. These data suggest a potentially different impact of concomitant BRI on HV vs. LV, which could affect clinical decision making.[Table: see text]

e14132 Background: The use of PD-1 inhibitors (PD1) has been limited due to the lack of prognostic markers of response. Previous studies have suggested that indirect inflammatory markers such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) may correlate with response to treatment and improved survival. We sought to evaluate the impact NLR and PLR in a real world cohort of patients (pts) with advanced solid tumors treated with PD1. Methods: Records of all pts treated with PD1 between 2011-2017 at the John Theurer Cancer Center were reviewed. NLR and PLR were registered at baseline and longitudinally. We dichotomized as low (lNLR/lPLR), and high (hNLR ≥5/hPLR ≥160). Univariate logistic regression and Cox proportional hazards were used for progression free survival (PFS), and overall survival (OS). Landmark analyses were performed at cycles 2 (C2), and 5 (C5). Results: 178 pts received 1131 cycles of PD1. Median age was 65 (range 24-93); 43% were female. ECOG was ≥1 for 85%. 142 pts (80%), and 89 (50%) received ≥2C and ≥5C respectively. In univariate analyses, baseline hNLR and hPLR were independently associated with inferior OS (median 7.8 vs 18.3 months; HR 1.77, 95% CI 1.21-2.43; p = 0.004), ) and (median 6.4 vs 15.6 months; HR 1.42, 95% CI 1.09-2; p = 0.04) respectively. On landmark analyses, lNLR and lPLR were associated with longer PFS and OS at 2C, and 5C. Longitudinally, lNLR and lPLR correlated with response rate; NLR decreased by 0.08 (95% CI: -0.19 to -0.04; p = 0.03) and PLR by 17 (95% CI: -29 to -14; p = 0.07) per month in responders compared with non-responders. hNLR or hPLR did not correlate with increase in autoimmune toxicities. Conclusions: hNLR, hPLR are adversely prognostic markers in pts receiving PD1 inhibitors in a “real world cohort”. These markers correlate with a longitudinal response and may help predict response. Further prospective studies are needed to determine their utility in decision making during treatment.

e16508 Background: BM in patients (pts) with CRPC correlate with higher mortality and costs. BRI zoledronic acid and denosumab are frequently used for the prevention of skeletal-related events (SRE) in pts with CRPC and BM. AA is the most common 1st line treatment for men with metastatic CRPC. We sought to evaluate the impact of BRI on time to first SRE (ttSRE) and OS of pts receiving 1st line therapy AA for CRPC with BM. Methods: We identified a cohort of men starting AA as 1st line therapy for CRPC with BM between 2013-2015 from 7 hospitals’ IRB approved registries. Pts were grouped by use of concomitant BRI and subgrouped by volume of disease (per E3805 definition) at AA start. The endpoints were OS, defined as time from AA start to death or last follow-up visit, and ttSRE. Results: Of the 338 pts included, 256 (76%) received AA alone and 82 (24%) AA+BRI. ECOG PS (PS) was ≥1 for 178 pts (52.7%). No statistically significant difference in ttSRE was found between the 2 cohorts [see Table]. Median follow-up for OS was 25.6 months. Pts receiving concomitant BRI showed a significantly longer OS and a 36% decreased risk of death compared to AA alone (HR = 0.64; 95% CI, 0.64 0.46-0.91; p = 0.012). Notably, OS in the AA alone group was shorter than commonly described. The OS benefit with BRI was greater for men with high volume disease (HV) (HR = 0.42; 95% CI, 0.25-0.71; p = 0.001). On MVA, BRI vs. no BRI, low volume of disease vs. HV, PS 0 vs. ≥1, baseline VAS pain ≤3 vs. > 5, and baseline PSA are independently associated with longer OS. Conclusions: Using a multicenter database, the addition of BRI to 1st line AA for CRPC men with BM and poor prognostic factors did not improve prevention of SRE. However, concomitant use of BRI and AA was associated with a significantly improved OS, particularly in HV. Further research to determine the driving factors is needed. [Table: see text]

e24026Background: Comprehensive genomic profiling to identify driver mutations for which effective therapies or clinical trials are available is part of the standard diagnostic evaluation for NSCLC...

93 Background: Tumor mutational load (TML) has been proposed as a biomarker of responsiveness to novel immune checkpoint inhibitors (ICIs) due its association with increased neoantigen formation and tumor immunogenicity. Gastrointestinal cancers (GICs) are generally insensitive to ICIs; therefore the aim of this study was to evaluate the TML, clinically relevant genomic alterations (CRGAs), and PDL-1 status of GIC patients (pts). Methods: We analyzed samples of pts with GICs using a multiplatform profiling tool (Caris Life Sciences, Phoenix, AZ). TML and CRGAs were calculated based on next generation sequencing and mutational load was stratified as high (≥17 mut/Mb), intermediate (8-16 mut/Mb), and low (≤ 7 mut/Mb). PD-L1 status was determined by IHC. Descriptive statistics and simple linear regression were used for analysis. Results: A total of 85 pts with GICs were analyzed. The median pt age was 65. 53% were males and 47% were females. Tumors were colorectal 51%, pancreatic 13%, esophageal 13%, gastric 9%, hepatobiliary 11%, anal canal 4%, and small intestine 1%. 80 cases (94%) had an adequate sample for profiling and TML was available in 59 cases (74%). Cases were 5% TML-high, 56% TML-intermediate, and 39% TML-low. The median TML was 9 mut/Mb and median CRGAs was 3. The most commonly detected CRGAs were TP53 (56%), APC (44%), KRAS (40%), ATM (18%) and PTEN (6%). A positive but very weak correlation was found between TML and number of CRGAs (R2 = 0.3). PD-L1 status was available in 74 cases (93%) with 86% being PD-L1 negative and 14% PD-L1 positive. PD-L1 expression was most commonly seen in esophageal (50%) and anal canal (30%) cancers. Among 57 tumors tested for both biomarkers, no correlation was found between a high TML and PD-L1 expression. Conclusions: TML varies among GICs, and higher TML scores were not associated with PD-L1 expression, but there was a weak correlation between TML and the number of CRGAs. Further analysis by stratification of GIC type and prognostic analysis to assess the correlation between TMB and response to ICIs is warranted.

594 Background: Given the heterogeneity of gastrointestinal cancers (GICs), molecular profiling is becoming part of the standard of care for many solid tumors. The aim of this study was to evaluate the molecular profile of patients (pts) with GICs using a multiplatform profiling tool and to assess how the pattern of detected molecular alterations could guide clinical decision-making in these tumors. Methods: We retrospectively analyzed samples of 85 pts with GICs via a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ) in order to evaluate clinically relevant genomic alterations (CRGAs) and clinically relevant biomarker expression (CRBs) in GICs. Results: A total of 85 pts with GICs were analyzed. 45 (53 %) were males and 40 (47%) were females. Tumors were colorectal 43 (51%), pancreatic 11 (13%) esophageal 11 (13%) gastric 8 (9%), hepatobiliary 8 (11%), anal canal 3 (4%), and small intestine 1 (1%). 80 cases (94%) had adequate sample for profiling. CRGAs were identified in 71 cases (89%) with a median of 3 CRGAs in the cohort. The most commonly detected CRGAs were TP53 45 (56%), APC 35 (44%), KRAS 32 (40%), ATM 14 (18%) and PTEN 5 (6%). The median number of CRBs was 9 and high expression levels were seen of mismatch repair biomarkers (MLH1, MSH2, MSH6, PMS2) in 45 (56%), TOPO1 in 44 (55%), PTEN in 27 (34%), TOP2A in 20 (25%), ERCC1 in 19 (24%), and both TS and TUBB3 in 17 (21%). Based on actionable CRGAs and CRBs, 94% of pts matched at least one FDA approved treatment with proven clinical benefit, with a median of 4 available therapies per pt. In addition, there was a median of 189 chemotherapy and 64 targeted therapy clinical trial opportunities available for these pts given the molecular blueprint of their GICs. Conclusions: Multiplatform molecular profiling identified a high frequency of actionable CRGAs and CRBs in GIC pts. This approach has the potential to aid in clinical decision-making by providing a stratification of beneficial therapeutic alternatives individualized to the molecular framework of tumor. Larger prospective studies are warranted to further investigate the impact of profiling guided treatment decisions on patient outcomes.

8044 Background: Racial disparities of FISH abnormalities in multiple myeloma (MM) have been well described in whites (W) but partially described in minorities (M) (Paulus et al, ASH 2016, 4432). We aimed to explore racial-based differences of FISH abnormalities using the largest cohort of m to date. Methods: CD-138 selected FISH was done on 799 consecutive patients (pts). Pts without symptomatic MM, and biopsy >6 months after diagnosis were excluded. The abnormalities evaluated included standard and intermediate risk: IGH rearrangements (IGH r), t(4;14), t(11;14), and high risk: t(14;20), t(14;16), del13q, del 17p, 1q21. Chi-square was used for statistical analysis. Due to smaller numbers, all m (Hispanic (H), Black (B), Asian (A) and Other (O)) were included into the same group for statistical analysis. Results: 482 pts were eligible, 343 (71%) were W, 52 (10%) H, 50 (10%) B, 19 (3%) A, and 18 (3%) O. Median age was 65 years, 54% were male, and 26% ISS stage 3. There were no were no statistically significant differences in FISH abnormalities between the m (Table1). Overall W had more abnormalities in IGH r, t(4;14), t(11;14), t(14:20), 1q21 gain compared to M. Most notably W had more IGH r (39% vs 28%; p=0.019) and t(11;14) (20% vs 12%; p=0.024). There were no statistically significant differences between W and m in the high risk FISH abnormalities. Conclusions: We had significant differences in FISH compared to M. W had more IGH r and t(11;14) than M, and there was no difference in high risk FISH abnormalities between W and M. This study confirms the biological racial disparities that exist in minorities with MM. Further studies with more inclusion of minorities are needed to elucidate these disparities and its effects on risk stratification and outcomes. [Table: see text]

e13521 Background: The use of next-generation sequencing (NGS) in clinical practice has increased the treatment (tx) options for cancer patients (pts). The expansion of genomic libraries used by NGS databases has resulted in increased identification of targetable genomic alterations (GAs). The aim of this study was to identify the clinical implications of genomic library expansion in the detection of GAs in pts with brain cancer at a large academic institution. Methods: We retrospectively analyzed 71 consecutive pts with brain cancer at the John Theurer Cancer Center that had NGS performed between 02/2014 and 09/2016. GAs were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number (n) of available genomic-directed tx and n of clinical trials were reviewed. The NGS assay interrogated 236 genes and introns of 19 genes until 09/2014, and subsequently was expanded to include 315 genes and introns of 28 genes. We compared median survival, n of GAs found, n of available trials, and n of tx available in pts who received NGS until 09/2014 (G1, n = 33) with pts who received NGS after 9/2014 (G2, n = 38). Results: Median survival was 30 months (range 19.9-40.1), median age was 62 years (range 26-82), the median n of GAs/sample was 5 (range 1-11). There was a significant positive correlation between n of GAs/sample and n of available trials and tx (r = .5, p = .00 and r = .3, p = .00, respectively). There was a negative correlation between survival and n of GAs (r = -.3, p = .02). G1 harbored 142 GAs with a median n of 4 GAs/sample (range 1-10), while G2 harbored 170 GAs with a median n of 5.5 GAs/sample (range 0-11). There was an absolute increase of 19.7% in GAs in G2 compared to G1. There was no difference in median overall survival. Conclusions: The expansion of genomic libraries increased the detection of GAs, and was positively correlated with the n of tx and clinical trials available for brain cancer pts. Survival was not affected by the expansion of the genomic library, but higher n of GAs was correlated with shorter survival. Expansions of NGS databases lead to increased n of potential tx options for brain cancer pts. Further studies are needed to investigate the impact of NGS targeted tx on survival.

e15722 Background: Pancreatic cancer (PaCa) is a highly lethal disease, with a 5-year overall survival (OS) rate of approximately 6%, and a median OS of only 3–6 months (m). Despite recent improvements in surgical techniques and increased use of combination chemotherapy (CT), OS remains poor. This study aims to examine the factors that led to increased OS in PaCa patients (pts) over the past two decades in a single academic institution. Methods: All medical records of pts diagnosed with PaCa at the John Theurer Cancer Center from 1990 to 2012 were reviewed, and 916 PaCa pts were included in this analysis. We compared one group of pts diagnosed from 1990 to 2003 (G1, n = 482), with a group of pts diagnosed from 2004 to 2012 (G2, n = 434) in terms of OS, demographics, tumor features and treatment (tx). Results: Median age at diagnosis was 70.5 years (range 26-96). There was no significant difference between G1 and G2 in terms of age at diagnosis, stage of disease and number of pts who received surgery. A significantly higher percentage of pts received CT in G2 compared to G1 (66.5% vs 51.0%, p = .00). Tumors of the pancreatic head were more common in G1 compared to G2 (51.8% vs 44.4% p = .02). More pts in G2 received two or more CT agents compared to G1 (49.0% vs 34.1%, p = .00). Median OS was significantly longer in G2 compared to G1 (9m vs 5m, p = .00), in pts who received CT compared to pts who did not (3m vs 9m, p = .00) and in pts who received surgery compared to pts who did not (5m vs 19m, p = .00). Pancreatic head location was associated with improved OS compared to other locations (9m vs 5m, p = .00). No OS difference was found between pts who received combination with two or more agents vs single agent CT. Conclusions: In line with multiple studies, analysis of PaCa data from our institution showed an increase OS in pts diagnosed with PaCa in more recent years, and in those who received surgery and CT. CT was administered in a larger number of pts in G2, which might account for the better OS in this group. Pts diagnosed with tumors of the pancreatic head had better survival, which could be explained by earlier presentation leading to earlier diagnosis and tx. Further research in PaCa therapeutics is needed, as long-term OS in PaCa pts remains poor despite recent advances.

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

e12037 Background: Increased use of comprehensive genomic profiling (CGP) has recently led to improved genomic characterization of tumors, increased access to individualized therapies and increased availability of clinical trials in breast cancer patients. The aim of this study was to evaluate the clinical impact of genomic profiling in breast cancer patients with the use of a CGP assay at a large cancer center. Methods: We retrospectively analyzed 101 consecutive breast cancer patients who received CGP at the John Theurer Cancer Center between 12/2011 and 08/2016. Genomic alterations (GAs) were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of available genomic-directed therapies and number of available clinical trials were reviewed. The CGP interrogated up to 315 genes and introns of 28 genes. Results: Median age at diagnosis was 58 years (range: 35-83 years). With a median follow-up of 189 months (range 1-189), median survival was 163 months (range 142-184). A total of 560 GAs were found in our population, with a median of 5.0 GAs/sample (range 0-16), a median of 2.0 therapies/patient (range 0-11), and a median of 11.0 clinical trials/patient (range 0-36). The most frequent GAs found were TP53 (47.5%, n = 48), PIK3CA (34.7%, n = 35), MYC (22.8%, n = 23), CCND1 (19.8%, n = 20), FGF3 (16.8%, n = 17), FGF4 (15.8%, n = 16), and ZNF703 (14.9%, n = 15). A significant positive correlation was found between number of GAs and the number of available targeted therapies and clinical trials (r = 0.5 and r = 0.7, p = 0.00, respectively). Increasing age is a predictor of having a PIK3CA mutation (OR = 1.05; CI:1.01-1.09, p = 0.00) while decreasing age is a predictor of having a MYC mutation by logistic regression (OR = 0.95; CI:0.91-0.95, p = 0.03). Conclusions: The systematic use of CGP led to the identification of a high number of GAs, which correlated with a median of 2.0 individualized therapies and a median of 11.0 clinical trials available for breast cancer patients. The clinical impact of genomic-directed individualized therapies needs to be further investigated in prospective, randomized studies.

803 Background: The routine use of comprehensive genomic profiling (CGP) has led to better genomic characterization, more personalized treatments and higher enrollment in clinical trials for many solid cancers. The aim of this study was to evaluate the clinical and genomic prolife of patients (pts) with gastrointestinal cancers (GIC) with the use of a CGP assay and their potential therapeutic benefit at a large comprehensive cancer center. Methods: We retrospectively analyzed 83 consecutive pts with GIC that had CGP at the JTCC between 01/2014-09/2016. Demographics, CGP results, and clinical characteristics were studied. Clinically relevant genomic alterations (CRGAs) were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA), and were defined as alterations linked to approved therapies and those under evaluation in genotype-driven clinical trials. Results: 83 pts with GIC were analyzed. 46.9% males and 53.0% females. The median age at diagnosis was 58.5 years. 73 (88%) patients were stage III/IV at diagnosis. Tumors consisted of colorectal (36%), gastric (24%), pancreatic (12%) and cholangiocarcinoma (6%). All the pts were found to have at least one genomic alteration (GA). CRGAs were identified in 63 (76%) of cases, with an average of 2 per pt. The most frequently identified GAs were TP53 43 (29.9%), APC 24 (16.7%), KRAS 31 (21.5%), ARID1A 12 (8.3%), PIK3CA 11 (7.6%), and SMAD4 11 (7.6%). Of the 63 pts with CRGAs, 23 (36%) received one of the therapies suggested by the NGS assay, and 9 (14%) were enrolled in a clinical trial. Conclusions: The use of CGP assay identified a high frequency of CRGAs in GIC pts. The assay provided information for genomic-directed therapy in 36% of the patients. The routine use of CGP in GIC may lead to pts receive more personalized treatments. The potential benefit of selected targeted therapies in individual cases suggests that larger studies of treatment guided by routine CGP in gastrointestinal malignancies are warranted.

774 Background: The use of next-generation sequencing (NGS) in clinical practice has increased the therapeutic options for many cancers. Multiple NGS assays are now commercially used. The genomic libraries used by these assays are continuously being expanded, resulting in increased detections of genomic alterations (GAs) leading to potential new treatments. The aim of this study was to identify the clinical and research implications of a database expansion in the detection of GAs in patients with gastrointestinal cancers (GIC). Methods: We retrospectively analyzed 83 consecutive patients with GIC that had NGS at the John Theurer Cancer Center between 01/2014 and 08/2016. GAs were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA). GAs, number of genomic-directed therapies and number of clinical trials were reviewed. Results: Period 1 (P1) comprised 01/2014-09/2014, period 2 (P2) comprised 10/2014-08/2016. The NGS assay interrogated 236 genes and introns of 19 genes during P1, and was expanded to 315 genes and introns of 28 genes during P2. The 21 samples analyzed during P1 harbored a total of 82 GAs with an average of 3.9 GAs/sample (range 1-7). The 62 samples analyzed during P2 harbored a total of 342 GAs with an average of 5.5 GAs/sample (range 1-20); representing an increase of 42% in GAs from P1 to P2. 41 GAs in 29 genes were detected in P2 that were not interrogated during P1. The average of genomic-directed therapies with potential clinical benefit increased from 1.8 during P1 vs 2.6 during P2 (44.4% increase in potential therapies). Based on new genomic findings, more clinical trials were made available during P2; an average of 8 vs 4 clinical trials (100% increase in available clinical trials). Conclusions: Periodical updates on NGS and the expansion of genomic libraries increase the detection of GAs, potential new genomic-directed therapies and available clinical trials. Continued expansions of NGS are needed to improve genomic characterization, and increase in the personalized therapeutic options for our patients with GIC.

791 Background: With the surge of drug development in the past decade, early phase clinical trials (EPCT) have gained value evaluating the potential benefits of new therapies. The inclusion/exclusion criteria in EPCT are usually rigorous and may exclude many patients (pts) commonly seen in clinical practice. Our objective was to identify the most common comorbidities excluded in EPCT for CRC. Methods: ClinicalTrials.gov was queried on December 1stof 2015. We reviewed the characteristics and eligibility criteria of 369 phase I/II interventional drug trials including: experimental arm therapy, location, and exclusion/inclusion criteria. Logistic regressions were completed and exclusion was studied as a binary variable. Results: Of the 369 trials, 68% were phase II and 32% phase I. 46% were conducted in the United States, 30% in Europe, 15% in Asia and 9% in other locations. 74 (20%) trials excluded pts > 70 years of age. 142 (39%) trials required creatinine levels < 1.5 mg/dl, liver enzymes (AST/ALT) < 2.5 and bilirubin < 1.5 of the upper limit of normal. Cytopenia was a significant exclusion factor: 147 (47%) trials required Hgb > 9 g/dl and 218 (59%) excluded pts with platelets < 100,000/dl. In terms of comorbidities, 98 (27%) trials excluded pts with heart failure (NYHA class 3/4), 74 (20%) with atrial fibrillation, 112 (31%) with any anticoagulation therapy and 155 (42%) with positive HIV. Trials located in the US were more likely to exclude pts with Hgb < 9g/dl (OR: 1.5, 95%CI: 1.1-2.3, p < 0.05), immunotherapy trials were more likely to exclude pts on any anticoagulation (OR:1.8, 95%CI: 1.2-2.8, p < 0.007) and targeted therapy trials were more likely to exclude pts with history of DVT/PE or cardiovascular diseases (OR: 3.4, 95%CI: 1.9-5.8, p < 0.0001; OR: 2.3, 95%CI: 1.3-3.8, p < 0.002, respectively). Conclusions: 20% of EPCTs on CRC excluded pts with advanced age, organ dysfunction and common comorbidities. Many of the EPCT reviewed were not inclusive of our aging oncology population who are more likely to have multiple comorbidities. Investigators should review whether sufficient justification exists for every exclusion criterion before their incorporation in future trial protocols.

e14053Background: CNS disease is common in multiple neoplasias, but clinical trials tend to exclude this patient population due to the increase in morbidity/mortality associated with CNS metastasis...

2529Background: Early phase clinical trials (EPCT) evaluate the potential benefits of new regimens and help guide the care of oncology patients (pts).The inclusion/exclusion criteria in EPCT are us...

534 Background: Surgical resection remains a mainstay of treatment for localized colorectal cancer (CRC). However, up to 35% of patients (pts) develop recurrence with a significant decrease in overall survival. The aim of this study was to evaluate clinical characteristics and specific predictors of recurrence for stage I/II CRC Methods: We performed a retrospective analysis of 2310 pts diagnosed with stage I/II CRC at our institution between 1990 and 2013, with a minimum follow up of 24 months. Tumor characteristics and recurrence data were studied. Cox regression was used for statistical analysis. Results: Of the 2310 pts, recurrence was identified in 276 (12%) pts, of which 88 (32%) pts had early recurrence ( < 1 year). Median time of recurrence was 625 days. 210 (76%) pts had local recurrence while 66 (24%) pts had distal recurrence, with liver being the main site of distant metastasis. Males had a higher recurrence rate than females (16% vs. 7%, p < 0.0001). When comparing recurrence pts (R) with non-recurrence (NR) pts, Hispanics were more prevalent in the R group (13% vs 8%, p < 0.01). R pts were more likely to have rectal and poorly differentiated tumors (33% vs. 13%, p < 0.0001; 23% vs. 14%, p < 0.0001, respectively). Mucinous adenocarcinomas were more prevalent in the R group (16% vs. 9%, p < 0.0005). In multivariate analysis: male sex (OR: 1.24, 95% CI: 1.21-1.56, p < 0.001), rectal tumors (OR: 4.2, 95% CI: 3.14-5.06, p < 0.001), tumor size (OR: 2.55, 95% CI: 1.31-4-51, p < 0.01), and positive margins (OR: 3.6, 95% CI: 2.13-5.21, p < 0.04) were independent predictors for recurrence. K-ras (+) status was a predictor of recurrence by univariate analysis. Age, race, and histologic grade were not predictors of recurrence. Pts with early recurrence had a lower median overall survival compared to pts that developed recurrence after 1 year, 37 months (95% CI: 26.6-49.6) vs. 59 months (95% CI: 42.4-74.3), p < 0.04. Conclusions: Pts with recurrence were more likely to have rectal and poorly differentiated tumors. Poorer survival was observed in pts with early recurrence. These findings could serve as important prognostic information and may help identify the pts that would benefit from aggressive surveillance after treatment.

10524 Background: Risk estimation of recurrence in localized GIST relies on factors as mitosis, size, site or capsule rupture. Recently, genotype has shown to add prognostic value at least in inter...

10529 Background: Pathogenesis in GIST could be related to cancer stem cell hypothesis (highly chemo resistant, very uncommon complete responses, kit is stem cell marker) even though no stem cell component in GIST has been yet demonstrated. Wnt signaling regulates proliferation in some normal and cancer stem cells as it occurs with intestinal epithelium. We have explored the prognostic significance of several Wnt signaling pathway and related molecules. To investigate the prognostic significance of β-Catenin, CDC25A, ROR2, p53, CUL4A, AKT-p and VEGFR-3 by immunohistochemical (IHC) analysis in TMA specimens of 101 non-gastric GIST. Methods: Data of diagnostic, therapeutic and follow-up procedures stem from the GIST Registry of GEIS. Cytoplasmic and/or membrane staining was deemed positive for ROR-2, VEGFR-3 and p-AKT antibodies whereas nuclear staining was positive for β-Catenin, CDC25A, CUL4A and p53 antibodies. IHC positive cases were considered if they displayed staining in at least 10% of cells. Statistical analyses for correlation of protein expression with known prognostic variables (mitoses, size) were performed with Mann-Whitney U test. Results: A subset of 101 non-gastric localized GIST patients was selected (90 intestinal, 15 others: mainly rectum and omentum). The median age was 62 y with gender distribution of 59M/42F and the median of follow-up was 36 months. The positivity for each protein was distributed as follows: ROR-2 63%, p-AKT 55%, β-Catenin 53%, VEGFR-3 22%, CDC25A 20%, p53 8% and CUL4A 7%. A statistically significant correlation was found between mitoses and β-Catenin (median 5 if negative/ 10 if positive, p=0.028); VEGFR-3 (median 5 if negative/21 if positive, p=0.002); CUL4A (median 6 if negative/60 if positive, p= 0.027). Additionally, tumor size was statistically correlated with VEGFR-3 (median 7 if negative/11 if positive, p=0.007). Conclusions: VEGFR-3, β-Catenin and CUL4A are correlated with the highest proliferative non-gastric GIST. These findings deserve further analysis and lead to potential new molecular therapeutic targets in GIST. This study was partially granted by Buesa Grant of GEIS.