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TPS817 Background: Metastatic disease remains a consistent challenge for patients with gastrointestinal (GI) malignancies. Multiple immune checkpoint inhibitors (ICI) have been FDA approved for several GI indications. Still, patients will progress on these therapies, either immediately or after initial response. Palliative radiation therapy (RT) is an effective treatment that can be delivered to symptomatic metastases. It also has been reported to lead to an abscopal effect, which is an induction of response in a distant tumor. This is thought to result from increased tumor immunogenicity, tumor microenvironment modulation, and immune cell recruitment. Thus, palliative RT could not only relieve symptoms, but also potentially reinvigorate the immune response, prolong ICI efficacy, and delay next-line systemic therapy that carries risks of unknown efficacy and tolerability. Ongoing studies seek to elucidate prognostic and predictive biomarkers of the abscopal effect. However, cohorts of patients with GI malignancies are limited, so there remains a need for research in combining RT and immunotherapy in the context of metastatic GI cancer. ARM-GI aims to study the radiation-augmented immune response in patients with metastatic GI cancers progressing on immunotherapy. Methods: ARM-GI is a phase 2, single arm study. Key eligibility criteria include confirmed metastatic GI malignancy, progressive disease per RECIST v1.1 on any ICI, and at least 2 metastases, one of which can be safely left unirradiated. The target prescription dose is 30 Gy in 5 fractions to symptomatic sites through intensity modulated RT or stereotactic body RT. Patients will continue the same immunotherapy after RT and be evaluated per RECIST v1.1 longitudinally. The primary endpoint is overall response rate (ORR) per RECIST v1.1. Secondary endpoints include ORR per iRECIST, progression free survival, overall survival, local control in radiated lesion(s), effect of distant radiation on unirradiated target lesions, incidence of new metastatic lesions, safety by CTCAE v5.0, and time to new systemic therapy. The study will enroll 28 patients, with recruitment ongoing. Serial peripheral blood samples are collected for exploratory studies that will analyze for association with disease response and quantification of changes in circulating immune cell subsets after RT compared to baseline. Clinical trial information: NCT04221893 .

3565 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. Methods: Single-center, phase 2 trial with safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts (NCT03396926). Key eligibility: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: Capecitabine 1000 mg/m2 PO BID D1-14 Q21 days (confirmed RP2D) plus pembrolizumab 200 mg IV D1 Q21 days and bevacizumab 7.5 mg/kg IV D1 Q21 days. Endpoints: Primary: Objective response rate (ORR) by RECIST 1.1. Key secondary: Safety, duration of response (DOR), progression-free survival (PFS), overall survival (OS). Results: From 04/2018-10/2021, 44 patients (pts) were enrolled. Overall: Median age 53 years (range 28-79); female 50%; Caucasian 61%. Liver metastases at enrollment 80%. Prior therapies: median prior lines of therapy 2 (range 1-5); PD on fluoropyrimidine-containing regimens 91%; prior exposure to bevacizumab 86%. Complete toxicity data are available for 36 off-treatment pts. Grade ≥ 3 treatment-related (tr)AEs occurred in 10 (28%) pts, including grade 3 immune-related AEs in 4 (11%) pts. All-cause serious (s)AEs occurred in 13 (36%) pts and trSAEs in 5 (14%) pts. (tr)AEs leading to dose interruptions, reductions, or delays occurred in 21 (58%) pts, most commonly palmar-plantar erythrodysesthesia syndrome in 17 (47%) pts. Disposition: of 44 pts enrolled, 35 were removed for PD and 1 was removed for treatment noncompliance; 8 treatment ongoing. ORR in 40 evaluable pts was 5% (95% CI: 0.6,16.9). Best response by RECIST 1.1: partial response (PR) in 2 (5%); SD in 26 (65%); PD in 12 (30%). 2 responders: DOR 12 and 15 months, both with liver metastases. Median follow up was 7 months (range 1-45), with median PFS 4.3 months (95% CI: 3.9, 6.1), PFS at 6 months 31.1% (95% CI: 19.2%, 50.4%), and median OS 9.6 months (95% CI: 6.2, 13). Median time on treatment was 5 months (range 1-26). Single cell RNA sequencing on a subset of paired pre- and on-treatment biopsies demonstrated changes in the frequency of dendritic cells. Conclusions: The combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. The ORR of 5% did not meet the prespecified target of ≥ 15%, however nearly a third of pts had PFS > 6 months. Immune profiling of tumor biopsies and peripheral blood is ongoing. Clinical trial information: NCT03396926.

444 Background: Immune checkpoint inhibitors (ICI) have limited activity as monotherapy in unselected patients with ABC; the objective response rate (ORR) of PEM was 5.8% in the multicenter phase 2 KEYNOTE-158 trial. GM-CSF modulates immune cells including monocytes and the innate immune response and has demonstrated safety and prolonged survival (OS) in combination with ipilimumab in melanoma. This phase 2 trial was designed to evaluate the efficacy and safety of PEM in combination with GM-CSF in ABC. Methods: Single-center, phase 2 trial with Simon’s 2-stage design and expansion cohort (EC) (NCT02703714). Key eligibility: ABC with progression/intolerance on ≥ 1 standard therapy, no prior ICI, bilirubin ≤1.5xULN. Treatment: PEM 200 mg IV Q21 days plus 2 cycles of GM-CSF 250 µg SC D1-14 Q21 days in cycles 2 and 3 (Stage 1 and EC) or in cycles 1 and 2 (Stage 2). Primary endpoint was objective response rate (ORR) by RECIST 1.1, H0 5% vs. H1 20%. Key secondary endpoints were safety, progression-free survival (PFS), OS, PD-L1 expression. Exploratory endpoints included relationship between efficacy outcomes and anatomic subsite, risk factors, and tumor genotype. Results: Overall, 42 patients enrolled between 5/2016-12/2019: n = 9 in Stage 1, n = 18 in Stage 2, and n = 15 in EC. Overall: median age 61; female 67%; intrahepatic (ICC) 67%, extrahepatic (ECC) 26%, gallbladder (GBC) 7%; stage IV 90%; hepatitis B/C virus positive (HBV/HCV+) 24%; microsatellite instability (MSI-H)/stable (MSS)/unknown n = 1/35/6. Immune-related (ir)AE occurred in 69%, grade 3/4 treatment-related (tr)AE in 10%, all-cause serious (S)AE in 36%, and trSAE in 7%. ORR was 12% (95% CI: 4, 26), with median PFS of 63 days (95% CI: 55, 125), PFS at 6 months in 27% (95% CI: 14, 43), and median OS 3of 93 days (95% CI: 243, 573). There was no significant difference in ORR, PFS, or OS by anatomic subsite or tumor PD-L1 expression; HBV/HCV+ showed trends toward higher ORR (30% vs 6%, p = 0.08) and longer median PFS (276 vs 63 days, p = 0.06) and OS (1033 vs 323 days, p = 0.052). Conclusions: The combination of PEM plus GM-CSF was safe and well-tolerated with higher ORR than expected for PEM monotherapy in a predominantly MSS ABC population but did not meet target ORR threshold for efficacy. ORR and median PFS and OS were highest in patients with underlying HBV or HCV infection. Immune profiling of on-treatment biopsies and peripheral blood are ongoing to ascertain influence of both PEM and GM-CSF on circulating and tumor immune microenvironment. Clinical trial information: NCT02703714.

42 Background: Diet may be associated with survival and health-related quality of life (HRQOL) among CRC survivors. Behavioral interventions using web and mobile technology are feasible and acceptable approaches to modify dietary behavior. Little is known about the effect of web-based dietary interventions on HRQOL among CRC survivors. Methods: The Survivor Choices for Eating and Drinking study (SUCCEED) was a pilot randomized wait-list controlled trial designed to determine the feasibility and acceptability of a 12-week (wk) web-based dietary intervention with daily text messages. In this secondary analysis, we estimated the effect of the intervention on HRQOL. Between 2017-2018, 50 CRC survivors were randomized (1:1) to intervention or control. Participants in the intervention arm received the intervention in wk 1-12 and were followed from wks 12-24. Participants assigned to the control arm for 1-12 wks had the option to receive the intervention in wks 13-24. In both arms, HRQOL and sleep quality were assessed using the EORTC QLQ–C30 and CR29 and the Pittsburgh Sleep Quality Index at 0, 12, and 24 wks. Within- and between-group mean changes in HRQOL from enrollment to 12 and 24 wks were evaluated using independent t-test and paired t-test. Results: Follow-up was 88% complete at 12 and 24 wks in the intervention arm and 92% and 80% complete at 12 and 24 wks in controls. Participants mean age was 56 ± 9 y; 34% were men, 70% identified as non-Latinx White, 12% identified as Latinx, and 70% had stage III cancer. Between 0 and 12 wks, an increase in emotional functioning was observed in the intervention arm [mean change: 9.1; 95% confidence interval (CI): 2.2,16.0], while a decrease in emotional functioning was observed in controls (mean change: -5.1; 95%CI: -14.5,4.1; between-group mean difference: 14.3; 95%CI: 3.0,25.6). Between 0 and 24 wks, an increase in social functioning (mean change in intervention: 12.1; 95%CI: 2.1,22.1; between-group mean difference: 13.8; 95%CI: 2.1,25.5) and a decrease in fatigue (mean change in intervention: -9.1; 95%CI: -17.1,-1.1; between-group mean difference: -4.1; 95% CI: -15.8,7.6) was observed in the intervention arm. No other measures of HRQOL or sleep quality differed within or between arms. Conclusions: A web-based dietary intervention with daily text messages may improve emotional and social functioning among CRC survivors. Further study to evaluate the effect of web-based interventions on HRQOL among CRC survivors in larger studies may be merited. Clinical trial information: NCT02965521.

3565 Background: Over half of patients (pts) with oligometastatic CRC treated with curative intent surgery or radiotherapy experience cancer recurrence with or without adjuvant chemotherapy. ctDNA detection post-definitive treatment could identify high risk pts for additional intervention to eliminate molecular residual disease. Here we report results of a prospective observational study aiming to determine ctDNA detection rates using a sensitive liquid biopsy and to correlate post-procedure ctDNA detection (post-ctDNA (+)) with radiographic mCRC recurrence. Methods: Pts with mCRC intending to undergo a curative intent procedure were prospectively recruited at two US sites. ctDNA was collected pre-procedure, 3 weeks post-procedure, and at multiple structured follow-up timepoints. The presence of ctDNA was evaluated using a plasma-only integrated genomic and epigenomic assay (Guardant Reveal, Guardant Health). A bioinformatic classifier was applied to differentiate tumor derived versus non-tumor derived cell-free DNA. Results: Among 52 enrolled pts, post-ctDNA data is available for 45 pts (87%), with a median of 4 (range 1-10) timepoints per pt. The sample analysis failure rate was 1% (2/217). As of 1/1/2021, the radiographic recurrence rate was 60% with a median follow-up time of 50 (range 4-192) weeks. 23 of 25 pts with post-ctDNA(+) have had recurrence (Positive Predictive Value [PPV], 92%). On average, ctDNA was detected 28 weeks before radiographic recurrence (mean 12 vs. 40 weeks, respectively). The two pts with post-ctDNA(+) but no recurrence have > 3 years follow-up; one pt received adjuvant chemotherapy and cleared ctDNA. With a median event-free follow-up time of 97 (range 4-192) weeks, 4 of 20 pts with no post-ctDNA detection (-) have recurred (Negative Predictive Value, 80%). 3 of 4 pts with recurrence despite post-ctDNA(-) also were pre-ctDNA(-). We observed a sensitivity of 85% and a specificity of 89% for the ctDNA assay. The median time to radiographic recurrence was 36 wks for ctDNA(+) vs. not reached for ctDNA(-) (Hazard Ratio, 7.7; 95% CI, 2.6-22.5; P

77 Background: MSS mCRC rarely responds to pembrolizumab monotherapy, but capecitabine and bevacizumab may induce immune-stimulatory effects. This study evaluates the safety, tolerability and preliminary efficacy of pembrolizumab in combination with capecitabine and bevacizumab in MSS mCRC. We present results at the planned interim analysis. Methods: Design:single-arm, open-label, single-site phase 2 trial with a safety lead-in to confirm the recommended phase 2 dose (RP2D) for capecitabine and expansion cohorts. Per the Simon’s 2-stage design, ≤1 response in 29 patients (pts) requires trial suspension. Key eligibility criteria: MSS mCRC with stable disease (SD) or progressive disease (PD) on prior fluoropyrimidine-based therapy. Treatment: RP2D PO capecitabine on days 1-14 plus 200 mg IV pembrolizumab and 7.5 mg/kg IV bevacizumab on day 1 in 21-day cycles. Pts are followed for toxicity and radiographic response. Results: From 04/2018-09/2020, 29 pts were enrolled, of whom 15 (52%) were female; 21 (72%) white; and median age was 55 years (range 36-77 years). Prior therapies: 2 (7%) pts had SD and 27 (93%) pts had PD on fluoropyrimidine-containing regimens; 24 (83%) pts had prior exposure to bevacizumab. The RP2D for capecitabine was 1000 mg/m2 PO BID, with no dose limiting toxicities observed. Complete toxicity data are available for 25 off-treatment pts. The most common related adverse events (AEs) were palmar-plantar erythrodysesthesia (PPE) (64%) and fatigue (68%). Grade ≥3 related AEs occurred in 9 (36%) pts, including immune-related AEs of Grade 3 dyspnea, hypophosphatemia, and pancreatitis in 1 pt each. Treatment related AEs leading to dose interruptions, reductions, or delays occurred in 15 (60%) pts, most commonly PPE in 13 (52%) pts. No pt had a related AE leading to treatment discontinuation or death. Disposition: of 29 pts enrolled, 24 were removed for PD and 1 was removed for an unrelated AE. Best response by RECIST 1.1 in 23 evaluable pts: partial response (PR) in 2 (9%); SD in 14 (61%); PD in 7 (30%). Median time on treatment was 6 months (range 2-26 months). Conclusions: Combination of pembrolizumab with capecitabine and bevacizumab was found to be tolerable with an expected toxicity profile in MSS mCRC pts. With 2 responses, the study met interim analysis criteria to continue accrual. Tissue and blood-based immune correlatives are planned. Clinical trial information: NCT03396926.

442 Background: There are no formal guidelines for the management of GI cancer pts with lung-exclusive or lung-predominant metastases (LM), which generally take a more indolent course than metastatic disease occurring at other anatomic sites. We performed a retrospective analysis at a high-volume tertiary care center to evaluate host and tumor characteristics of this pt population, describe treatment approaches, and model patterns and rates of growth. Methods: Eligible pts were identified through Cancer Center registry data, provider recall, and electronic record review. Criteria included LM occurring either synchronously (SLM) or metachronously (MLM) w/primary cancer diagnosis; nodal, but not visceral or peritoneal, mets allowed. Data re: demographics, tumor characteristics, and rx modalities were collected. We reviewed all eligible CT +/- PET scan reports to gather data on #, location, and size of pulm mets, with all images subsequently reviewed by an independent radiologist. Up to 5 pulm mets were tracked through each pt’s clinical course. Growth rate was estimated using a linear mixed model analysis considering patients as the random. Results: Forty pts were identified between 9/2009 - 12/2019 (23 F/17 M; 28 white/7 Asian/5 other/multi; median age 62 y.o.; n = 15 w/tobacco hx). Tumor types: pancreatic (n = 18), colorectal (n = 12), hepatobiliary (n = 7), other (n = 3). SLM vs MLM:13/27; intact vs resected primary = 16/24. Median time from orig cancer dx to onset of MLM = 16 mos (range, 1 to 60 mos). No. of pulm mets at 1st appearance: 1 (n = 7); 2-5 (n = 17); 6-10 (n = 16). Median size of largest pulm met at 1st appearance = 6 mm (range, 0-39 mm); avg growth rate of largest pulm met = 0.18 mm/month (95% CI, 0.08-0.27). Avg growth rate of up to 5 largest lesions (sum) = 0.35 mm/month (95% CI, 0.07-0.64). Median f/u time prior to rx initiation for MLM = 172 days (range, 25-1547 days); 18 pts developed additional mets during their observation period. Rx modalities for LM: surg (n = 6), radiation (n = 18), systemic rx (n = 32). Addn details specific to cancer type, progression patterns, and pt outcomes will be presented at the meeting. Conclusions: The natural hx of LM varies across the spectrum of GI malignancies. Further larger-scale efforts to define patterns of growth of LM for different GI cancers, informed by size, #, and clinical/molecular features, are needed to guide appropriate timing and selection of rx as well as surveillance strategies.

1573 Background: Prior studies have shown an increase in the rate of colorectal cancer (CRC) in young individuals in the United States. However, few studies have evaluated the health disparities that exist in this population, particularly using large, national cohorts. We examined differences in age, race, stage, region, and tumor location in younger and older patients with CRC. Methods: Data were extracted from the United States Cancer Statistics (USCS) for individuals diagnosed between 2001 and 2014. CRC incidence data among individuals < 50 years old were compared to those > 50 years old. Age-specific and age-adjusted incidences and trend analyses reported as annual percent change (APC) were performed using SEER*Stat and Joinpoint regression. Results: Of 1,886,441 individuals, the overall age-adjusted incidence of CRC decreased from 52.59 (per 100,000) in 2001 to 35.22 in 2014, with an APC of -3.24. Although over 35% cases were diagnosed in the Southern United States, the Northeast had the highest age-adjusted incidence at 45.26 per 100,000 patients. Younger patients were diagnosed with distant disease at 25.8% compared to only 18.4% in older patients. Younger patients were also more likely to have sigmoid or rectal cancers compared to older patients (64.3% vs. 45.7%). Of the 170,244 individuals < 50 years, 90,855 (53.4%) were men and 79,389 (46.6%) were women. The age-specific incidence in this younger cohort increased from 5.63 to 6.48 between 2001-2014, with an APC of +1.24 in 2001-2008 compared to +2.55 in 2012-2014. The incidence of CRC in patients aged 0-29, 30-39, and 40-49 years was 0.41 (per 100,000), 6.08, and 21.09, respectively. Black individuals < 50 years had the highest age-specific incidence of CRC (7.16 per 100,000) compared to Asian (6.43), White (6.07), or Hispanic (4.76) individuals. Conclusions: Our data suggests that CRC is increasing in young patients, particularly for those between 40-49 years and Black individuals. In our younger cohort, CRC was more commonly found in the sigmoid colon and rectum compared to older patients. Further research is warranted to direct resources towards improved colonoscopy or sigmoidoscopy screening for younger patients at risk.

110 Background: Clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) is limited by extrahepatic disease progression. TAS-102 (trifluride and tipiracil) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. We aimed to evaluate the safety of the combination of TAS-102 and 90Y resin TARE in a Phase I dose-escalation trial. Methods: Adult patients with bilobar liver-dominant chemo-refractory mCRC were treated with sequential Y90 resin TARE (body surface area dosimetry) in combination with TAS-102 (20mg/m2, 27mg/m2, and 35mg/m2) in 28-day cycles according to 3+3 dose-escalation design. Beginning with cycle 3, TAS-102 was administered as monotherapy until disease progression or development of intolerable toxicity. Primary objectives were to determine maximum tolerated dose (MTD) of TAS-102, to assess toxicity, and to establish safety of TAS-102 in combination with 90Y TARE. Results: A total of 14 patients (10 women, 4 men) have been treated to date. Among 9 patients enrolled in the dose-escalation phase, no dose limiting toxicities were observed. The MTD of TAS-102 in combination with Y90 was 35mg/m2, which was selected for the dose expansion phase. Severe adverse events (AEs) included: neutropenia (46%); anemia (23%); and thrombocytopenia (8%), which were attributed to TAS-102. All other AEs were mild and transient. At least one follow-up imaging study has been obtained for 13 patients, and 10 patients have completed trial participation. Disease control rate in the liver was 100%. Conclusions: The combination of TAS-102 and 90Y TARE for patients with liver-dominant mCRC is safe and consistently achieved disease control within the liver. Severity and incidence of AEs is within the expected range of TAS-102 and 90Y TARE monotherapy. A dose-expansion phase with planned enrollment of 12 patients is ongoing. Clinical trial information: NCT02602327.

3572 Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p < 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p < 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking < 50 days to complete treatment (p = 0.03), and < 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 < 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.

552 Background: Over half of patients (pts) with oligometastatic CRC treated with definitive surgery or radiotherapy experience cancer recurrence. Early detection of ctDNA could identify high risk pts for additional intervention to eliminate micrometastatic disease. Here we report interim results of a prospective study aiming to determine ctDNA detection rates using a sensitive multigene assay and to correlate post-procedure ctDNA detection with radiographic mCRC recurrence. Methods: Pts with mCRC intending to undergo a curative intent procedure were prospectively recruited at a single site. ctDNA was collected pre-procedure, 3 weeks (wks) post-procedure, and at multiple follow-up timepoints. ctDNA detection utilizing a multi-gene sequencing panel (Guardant Health) included somatic variant and epigenetic assessments. A novel variant classifier was applied to differentiate tumor derived versus non-tumor derived alterations. A Simon’s two-stage design with planned interim analysis to assess 3wk post-procedure ctDNA detection rate was employed. Results: Of 25 pts enrolled, 21 (84%) had evaluable paired pre- and post-procedure samples. In these 21 pts, the 3 wks post-procedure sample was collected after surgery (N = 20) or radiation (N = 1) to address liver (N = 17), lung (N = 3), or ovarian (N = 1) metastases ± colon resection (N = 6). ctDNA was detected (+) in 15/21 (71%) pre- and 11/21 (52%) post-procedure samples. ctDNA was (+) in 8/12 (67%) pre- and 8/17 (47%) post-procedure samples with carcinoembryonic antigen < 5 ng/ml. Conclusions: In this interim analysis of pts with mCRC undergoing curative intent procedures, the post-procedure ctDNA detection rate was 52%. The similarity between the observed post-procedure ctDNA detection and expected recurrence rate suggests promise for recurrence prediction using this approach. Given post-procedure ctDNA was (+) in > 3 pts, the study will continue to enroll, and pts are being followed for future correlation of ctDNA with radiographic recurrence. [Table: see text]

242 Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that typically account for < 5% of tumors arising in any organ site. Both the low incidence and heterogeneity contribute to the paucity of epidemiologic data regarding risk factors. However, evidence suggests that incidence rates in the U.S. are rising. We aimed to further characterize the burden of NENs in California. Methods: Using data from the California Cancer Registry (CCR), we identified all newly diagnosed NENs arising from pulmonary (including SCLC) and gastrointestinal (GI) sites from 1992-2015. We estimated age-adjusted incidence rates (AIR) standardized to the 2000 U.S. census population. We calculated annual percent change (APC) in AIRs using Joinpoint regression and compared AIRs by sex, race-ethnicity, primary tumor site, and county of residence categorized as urban, suburban or rural using SEER∗Stat. Results: From 1992-2015, 97,398 NENs were reported, with 40,099 GI (not lung or bronchus). Overall AIR was 12.5 per 100,000 person-years. Most NENs were of pulmonary (AIR 7.6) or colorectal (AIR 1.3) origin. Females had lower AIR with IR ratio (IRR) vs. males (0.80 95% CI 0.79-0.81). However, females had higher rates of gastric (IRR 1.22 95% CI 1.12-1.32) and appendiceal (IRR 1.19 95% CI 1.07-1.33) primaries vs. males. Compared to non-Hispanic (NH) whites, NH blacks had an IRR of 1.06 (95% CI 1.03-1.09), Asian/Pacific Islanders had an IRR of 0.46 (95% CI 0.45-0.48), and Hispanics had an IRR of 0.57 (95% CI 0.56-0.58). For all NEN subtypes, we estimated lower rates for residents of urban counties (IRR 0.83 95% CI 0.80-0.86) and suburban counties (IRR 0.94 95% CI 0.90-0.97) vs. rural counties. However for GI NENs, we estimated higher rates for residents of suburban counties (IRR 1.11 95% CI 1.03-1.18) and urban counties (IRR 1.10 95% CI 1.03-1.18) vs. rural counties. We found that rates of pulmonary NENs decreased since 1992 (APC -2.6), but rates increased in colorectal (APC 3.9) and all other GI primaries (all APCs ≥ 2.8). Conclusions: Based on these results we conclude that incidence rates for GI NENs reported to CCR steadily increased from 1992-2015. Residence in a suburban or urban county was associated with increased incidence of GI NENs. Additional analyses are ongoing.

11008Background: As interest in global oncology increases, the need to support early career investigators is a priority, as advocated by the ASCO Global Oncology Leadership Task Force. The Global C...

4087Background: The efficacy of immune checkpoint inhibition (CPI) has not been established in ABC. The combination of CPI plus the myeloid cytokine GM-CSF was safe with prolonged overall survival ...

180 Background: The number of individuals living after a diagnosis of gastrointestinal (GI) cancer is increasing. Emerging data suggest modifiable lifestyle factors impact survival after colorectal cancer (CRC), however very little is known about survivorship in other GI cancers. Given the common thread of multimodality therapy among many GI cancer survivors, there is a paucity of data on sexual function, fertility, anxiety/depression, changes in comorbidities, and quality of life after cancer treatment. Additionally, existing cohort studies of GI survivors are primarily European, and further data are needed from survivor populations in the US . Methods: Patients of the University of California, San Francisco GI Oncology Survivorship Clinic who are designated disease-free are recruited by mail or in clinic. We send secure online questionnaires to participants every six months for five years and annually thereafter. At varying intervals, questionnaires solicit sociodemographics, diet, physical activity, fertility, medical and smoking history, fear of cancer recurrence, sexual health, quality of life, psychological well-being, and sleep quality. Pathoclinical disease characteristics, treatment, and recurrence status are abstracted from the medical record at baseline and updated annually. Results: Between February and August 2017, 111 patients were enrolled; 68% of participants completed ≥1 and 57% completed all baseline questionnaires. Most patients had a history of colon cancer (52%, n = 58) or rectal cancer (31%, n = 34). Other diseases include: anal cancer (12%, n = 13), gastrointestinal stromal tumor (3%, n = 3), and other GI cancers (3%, n = 3). Fifty-eight percent of patients were female, 76% identified as white and median age at diagnosis was 55 (range 20-81). Median time from initial GI cancer diagnosis to study entry was 27 months. Following the initial recruitment wave of established patients, the average rate of enrollment is ~3 patients/week. Conclusions: Results from this ongoing cohort study will improve our understanding of modifiable risk factors for GI cancer recurrence and key survivorship issues related to psychological well-being, sexual function, fertility management, and quality of life.

168 Background: There are over 1.3 million colorectal cancer (CRC) survivors in the United States, and many of whom suffer from lower health-related quality-of-life (HRQoL) years after diagnosis and treatment. Physical activity may improve survival outcomes and HRQoL for CRC survivors. Feasible interventions to support physical activity after CRC diagnosis are needed. Methods: We conducted a two-arm randomized controlled trial of 41 men and women who had completed treatment for CRC. Participants in the intervention arm were given a Fitbit Flex™ and received daily text messages for 12 weeks. HRQoL was assessed in both arms at baseline and 12 weeks using the RAND Short Form Survey (SF-36) and the Functional Assessment of Cancer Treatment – Colorectal (FACT-C). Survey score changes from baseline to 12 weeks were compared between the two arms using independent t-tests, and scores at baseline and 12 weeks were compared using paired t-tests. SAS was used for analysis, and statistical significance was declared at p < 0.05. Results: We observed a statistically significant increase in the FACT-C functional well-being sub-scale in individuals in the intervention arm pre- and post- intervention (mean ∆ 1.81 ± 2.76; p: 0.02). There was no change in functional well-being in the control arm (mean ∆ -0.35 ± 4.12; p: 0.71). The between-arm comparison of change from baseline to 12 weeks was not statistically significantly ( p: 0.08). There was a statistically significant increase in the FACT-C emotional well-being sub-scale in the control arm (mean ∆ 1.20 ± 2.48; p: 0.04) and in the SF-36 role physical sub-scale in the control arm (mean ∆ 22.5 ± 38.8; p: 0.02). No other measures of HRQoL were statistically significantly different within groups, across time points, or between groups. Conclusions: A 12-week physical activity intervention using a Fitbit Flex and daily text messages may improve functional well-being among CRC survivors. Larger randomized studies are needed to definitively determine if a digital physical activity intervention improves functional well-being among CRC survivors, and if the improvement can be sustained over time. Clinical trial information: NCT02966054.

779 Background: As overall survival (OS) with metastatic colorectal cancer (mCRC) and imaging modalities improve, detection of ovmets may be increasing. The ovary is often a sanctuary site for mCRC; however, there is a paucity of data to guide decision-making regarding the role for oophorectomy. Methods: This is a single-institution retrospective review of patients (pts) who received care for mCRC (incl. appendiceal primaries) with ovmets from 2009-2017. Pts were identified through a hospital-based cancer registry, provider recall, and pathology and radiology databases. Clinicopathologic and treatment data were abstracted. Cox proportional hazards models were used to evaluate for associations with OS. Results: Of 108 pts, median age was 50 (range 19-106), 62 (57%) were Caucasian, and 69 (64%) had ovmets at initial CRC diagnosis. Primary tumor location was left-sided in 54 (50%), right-sided in 27 (25%), appendiceal in 18 (17%), and unknown in 9 (8%). Median OS from diagnosis of mCRC was 29.6 months (mo) with median follow-up of 21.9 mo (range 0.77-172.47). Younger age, absence of signet-ring or mucinous features, well/moderately differentiated grade, and resection of primary tumor were associated with improved OS (p < 0.05). Of 83 (76%) pts who underwent oophorectomy median OS was 36.7 mo vs. 25 mo in those who underwent non-operative management (HR 0.54, 95% CI 0.31-0.94, p = 0.03). Among 94 pts with extra-ovarian disease, 70 (74%) underwent oophorectomy; however, no significant difference in median OS was detected vs. those who did not (30.9 vs 25.0 mo, p = 0.07). In a multivariate model, oophorectomy was not associated with OS (HR 0.63, 95% CI 0.29-1.36, p = 0.24). Conclusions: While ovmets have been previously reported as associated with a poor prognosis, the median OS for this cohort was comparable to existing OS data for mCRC pts. Although oophorectomy for ovmets from mCRC was associated with improved OS in univariate analysis, this effect was not significant in the presence of extra-ovarian metastases. Ovmets from mCRC remain a difficult challenge in clinical care. Oophorectomy may improve OS in select cases; however, further evaluation of predictors of benefit is needed.

386 Background: The efficacy of immune checkpoint inhibition (CPI) has not been established in ABC. GM-CSF modulates immune effector cells and has demonstrated safety and improved survival (OS) in combination with ipilimumab in melanoma. This phase 2 trial aims to evaluate the efficacy and safety of PEM in combination with GM-CSF in ABC. Methods: Design: Simon’s 2-stage. Key eligibility: ABC with progression/intolerance on ≥ 1 standard therapy, no prior CPI, bilirubin ≤1.5xULN. Treatment: PEM 200 mg IV Q21 days plus 2 cycles of GM-CSF 250 µg SC D1-14 Q21 days in cycles 2 and 3 (Stage 1 Safety Cohort) or in cycles 1 and 2 (Stage 2). Endpoints: 1◦: Progression-free survival at 6 months (PFS6) with H0 25% vs. H1 50%. Key 2◦: Safety, overall response rate (ORR) and duration (DOR), OS, PD-L1 expression. Exploratory: PBMC and tumor immune cell profiles, tumor genotype, microsatellite (in)stability (MSI or MSS). Results: Accrual has completed with 27 patients (pts) enrolled 5/2016-6/2017: F/M 13/14; median age 61 (range 37-77); intrahepatic 19 (70%), extrahepatic 7 (26%), mixed 1 (4%) cholangiocarcinoma; stage IVA/B 85%, II/III 15%; median prior therapies 2 (range 1-6). Adverse events (AE): Related grade(Gr) ≥3 AE occurred in 4/27 (15%) pts including immune-related (ir)AE of Gr4 diabetes mellitus and Gr3 thrombocytopenia in 1 pt each. Gr≤2 irAE in ≥5% were: arthralgia (33%), dry eye/mouth (15%), hyperthyroid/thyroiditis (15%), hypothyroid (15%), neuropathy (11%), rash (11%), and adrenal insufficiency (7%). Steroids were required in 3/27 (11%) pts. Disposition: 19 pts removed for PD, 1 for Gr2 irAE; 7 pts remain active on treatment. Median time on treatment: 6 cycles (range 2-22+). Best response by RECIST 1.1: Partial response (PR) in 5/24 (21%) evaluable pts (1 MSI, 4 MSS); minor regression and ≥50% CA 19-9 decline in 2 additional MSS pts for 11+ and 16+ months. PBMC analyses show changes in expression of activating and inhibitory markers including PD-1 on various immune cell populations. Conclusions: PEM plus induction GM-CSF is safe and tolerable in ABC. Durable radiographic and tumor marker responses including MSS pts warrant further study. PFS6, OS, and correlative analyses are ongoing. Clinical trial information: NCT02703714.

615 Background: Over 1.3 million people in the US are living with CRC. Physical activity is associated with lower risk of CRC mortality. Interventions are needed to increase physical activity after CRC diagnosis. Methods: We conducted a pilot RCT to determine the feasibility (adherence, attrition) and acceptability of a 12-wk intervention using a Fitbit Flex™ and daily text messages to increase physical activity after CRC. Eligible patients had to have colon or rectal cancer of any stage, be disease free or have stable disease, able to speak and read English, and access to Internet and a mobile phone. Individuals with contraindications to moderate-to-vigorous physical activity (MVPA) or exercising ≥30 min ≥5 d/wk were excluded. We explored the impact of the intervention (n = 20) vs. usual care (n = 21) on MVPA via ActiGraph GT3X+ accelerometers pre-/post-intervention. Results: The intervention was feasible and acceptable. On average, participants were 54 y, BMI 28 kg/m2 and enrolled 1.5 y after diagnosis; 59% were women, 73% were White, and 61% were stage III. The intervention arm wore their Fitbits a median of 74 d (89% of study days, IQR: 23-83 d) and responded to 74% (34) of the 46 text messages that asked for a reply (IQR: 28-82%). Older participants were more likely to wear the Fitbit ( r: 0.72; p < 0.001). Married participants were more likely to wear the Fitbit and respond to texts compared to unmarried (96% vs. 32% wear time, p: 0.02 and 85% vs. 46% response rate, p: 0.006). Most patients (88%) reported that the intervention motivated them to exercise and that they were satisfied with their experience. On average, the intervention arm increased MVPA by 14 min/d, while the control arm increased by only 1 min/d, but there was no statistically significant difference in change in MVPA between groups (mean difference comparing change in MVPA in the intervention vs. control: 13 min/d; 95% CI: -14, 40; p: 0.33). Conclusions: A 12-wk physical activity intervention with a Fitbit and text messages is feasible and acceptable among CRC patients after treatment. Larger studies are needed to determine whether the intervention increases physical activity. Clinical trial information: NCT02966054.

e15689 Background: Carcinoid crisis is a life-threatening event caused by release of vasoactive substances from neuroendocrine tumors (NETs). Octreotide is often used in the periprocedural setting as prophylaxis against carcinoid crisis; however, there is no standardized protocol for its use. We aimed to describe the periprocedural management of patients with metastatic NETs who underwent liver-directed procedures at UCSF. Methods: We identified 54 patients with NETs with hepatic metastases who underwent either liver resection/ablation (n = 30) or liver-directed embolization (n = 24) between 2012 and 2016. Anesthesia records and clinical data were abstracted. Carcinoid crisis was defined by physician documentation. Hemodynamic instability was defined as ≥10 minutes of systolic blood pressure < 80 mmHg or > 180 mmHg or heart rate > 120. Pearson chi-squared tests were used to test associations with three outcomes: crisis, instability, or none. Results: Three (6%) patients were documented to have developed carcinoid crisis. Another 14 (26%) patients developed hemodynamic instability. Of 16 patients who received preprocedural octreotide, 1 (6%) had a carcinoid crisis and 5 (31%) developed hemodynamic instability. History of carcinoid syndrome, degree of hepatic involvement, and use of pre or intraprocedural octreotide were not associated with carcinoid crisis or at least hemodynamic instability. Patients undergoing embolization were less likely to develop hemodynamic instability versus those undergoing liver resection (17% vs 43%, Pearson chi-squared p = 0.04). Conclusions: Occurrence of documented carcinoid crisis was low in this high-risk population. However, a significant proportion of patients developed hemodynamic instability, suggesting that carcinoid crisis is a spectrum diagnosis and may be clinically under-recognized. Use of octreotide was not associated with risk of carcinoid crisis or hemodynamic instability; however, this analysis was limited by our modest sample size at a single institution. There remains a need to establish an objective definition of carcinoid crisis and to inform standardization of periprocedural use of octreotide for at-risk patients.

6575 Background: Misconceptions about the curative potential of PC are common, and may arise from gaps in informed consent. Another contributing factor could be patients’ desire, or lack of desire, for information about prognosis and PC outcomes. Methods: We surveyed 137 patients with advanced colorectal (N = 102) or pancreatic cancer (N = 35) within 2 weeks of consultation about 1st or 2ndline PC, as part of randomized trial of a PC education intervention at 6 US sites. Patients rated how much information they wanted about PC risks/benefits, including impact on prognosis. Responses ranged from no information to as much as possible on a 5-point Likert scale. They reported decision-making preferences; whether a doctor discussed curability, and how likely they thought PC was to cure their cancer. Chi square and Wilcoxon tests examined whether information and decision-making preferences, or curability discussions were associated with expectations of cure. Multivariable logistic regressions evaluated whether associations were modified by age, race, gender, marital status, or cancer type. Results: Only 44.5% of patients accurately reported that their cancer was not at all likely to be cured by PC. Most patients wanted a lot, or as much information as possible about PC risks/benefits, including likelihood of cure (81.7%), cancer control (84.7%), and impact on length of life (80.3%). Most patients preferred shared (70.8%) versus active or passive decision-making. Neither decision-making nor prognostic information preferences were associated with expectations of cure. Patients (13.9%) who did not recall curability discussions were less likely to have accurate expectations (21% v 48%; OR, 0.29; 95% CI, 0.07-.97). Patient characteristics did not significantly confound this association. Conclusions: Most patients value shared decision-making and want maximal information about PC risks/benefits, including impact on prognosis. Despite wanting prognostic information and reporting curability discussions, many patients report inaccurate expectations about cure from PC. Future studies should examine whether these assertions reflect misunderstandings, differences in belief, or expressions of hope.

166 Background: Colorectal cancer (CRC) survivors can improve their quality-of-life (QOL), and potentially survival, by engaging in physical activity. The aim of this pilot randomized controlled trial (RCT) is to determine the feasibility of a technology-based physical activity intervention for CRC survivors. Methods: 40 CRC survivors will be randomized (1:1) to a 12-week physical activity intervention (Fitbit Flex, daily text messages) or usual care. Eligible individuals must: 1) have stage I-III colon or rectal adenocarcinoma; 2) have completed therapy; 3) be considered cancer-free; 4) be English speaking; 5) have no contraindications to moderate physical activity; 6) engage in < 150 min/week of moderate physical activity; and 7) have Internet and a phone that can receive text messages. Our primary outcomes are adherence (e.g., Fitbit wear time, text response rate) and acceptability assessed via survey. Secondary outcomes include change in physical activity via 7-days of ActiGraph GT3X+ accelerometers and QOL. Results: We have screened 350 individuals with stage I-III CRC at the University of California, San Francisco (UCSF) for eligibility. Of these, 181 (52%) were not eligible [non-English speaking (46%), ≥ 150 min/week of physical activity (22%), contraindications to physical activity (22%), not cancer-free (7%), did not own a mobile phone (2%)]. We invited the remaining 169 eligible CRC survivors to participate by mail, e-mail, phone, or in clinic; 76 (45%) actively declined and 59 (35%) did not respond after up to 3 contact efforts. As of October 2016, 34 CRC survivors have been randomized to intervention (n = 16) or control (n = 18). These individuals are: 55% female; 64% Non-Hispanic White; 73% have a 4-y college degree; and 64% work full-time. The median (IQR) age and BMI are: 56 (50, 65) y and 26.4 (23.2, 32.4) kg/m2, respectively. Conclusions: The results of this pilot study will inform a definitive RCT to determine whether a technology-based physical activity intervention improves QOL and survival after CRC diagnosis. Funding: This research was supported by the NIH (K07CA197077, KL2TR000143), Mt. Zion Health Fund and UCSF Helen Diller Family Comprehensive Cancer Center.

793 Background: A growing body of literature suggests that 25-hydroxyvitamin D [25(OH)D] levels are inversely related to the risk of developing CRC and that deficiency is associated with CRC-specific mortality. Due to the unique racial-ethnic diversity and UV exposure patterns of the San Francisco Bay Area, we aimed to evaluate vitamin D levels among our CRC patients at time of diagnosis and during treatment. Methods: Permanent residents of the SF Bay Area with a new diagnosis of CRC of any stage were recruited between 2011 and 2015 prior to initiation of therapy. Self-reported data on sun exposure, diet, and exercise patterns were collected. Clinical data including disease stage and primary tumor location were abstracted from charts. Serum 25(OH)D levels at time of diagnosis and at 6-month follow-up were batched and measured using the Liaison XL assay (Heartland Assays). Supplement use was not restricted. Kruskal-Wallis and Pearson correlation tests were used for categorical or continuous variables, respectively, to evaluate the associations of patient characteristics with 25(OH)D levels. Results: Among 94 patients with a new diagnosis of CRC, median 25(OH)D level at baseline was 27.0 ng/mL (range 7.2-59.0); 26% had deficient levels (

554 Background: BRAF mutation status and location of CRC primary each correlate with pattern of metastatic spread. We sought to determine whether presence of a BRAF V600E (BRAF) mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location. Methods: 40 patients with BRAF mutant mCRC were matched to 80 patients with BRAF wild-type CRC by location of primary tumor (right colon, left colon or rectum), sex, and age ( < 50; 50+). CT scans were reviewed for disease characterization. BRAF mutation status, clinicopathological characteristics, and sites of metastatic disease were associated using proportion tests. Results: Of the 120 matched patients,60% were female. The distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Median age at diagnosis was 57, range 20-88 yrs. Significantly higher frequencies of peritoneal metastases (p = 0.045) and ascites (p = 0.0038) occurred in patients with BRAF mutant tumors. Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. In patients with left colon primaries, BRAF mutations associated with less frequent liver metastases (42% vs. 79%, p = 0.024) and more frequent ascites (58% vs. 12%, p = 0.0038). Disease was not measurable by RECIST version 1.1 criteria in 20% of patients with BRAF mutations, most often with peritoneal metastases and ascites. Conclusions: Presence of a BRAF V600E mutation associated with a greater proportion of peritoneal metastases and ascites, even among patients matched for primary tumor location. Of 20 patients with BRAF mutant mCRC and peritoneal metastases plus ascites, 6 patients (30%) had disease that was not measurable by RECIST version 1.1. Radiographic characterization provides a window on BRAF mutant mCRC biology and also reveals a challenge for response evaluation on clinical trials. [Table: see text]

263 Background: The goal of post-treatment surveillance of CRC patients is to identify recurrences among patients eligible for salvage surgery or palliative chemotherapy. However, patient ineligibility for treatment of recurrence may contribute to variation in surveillance practices. The aim of this study was to evaluate patient factors that affect clinician decisions regarding surveillance and salvage treatment eligibility among CRC patients. Methods: A custom 41-item survey was developed, incorporating modified criteria for adult comorbidity evaluation. A convenience sample of physicians who treat CRC was recruited from the ALLIANCE GI Cancer Committee. All participants completed an anonymous written survey of objective and subjective information about salvage treatment eligibility and the impact on surveillance in these patients. Results: Respondents were medical oncologists (n = 16; n = 11 with > 10 yrs experience) and surgical oncologists (n = 4). Patients with average comorbidity were considered ineligible for curative salvage surgery at median age 85 yrs (IQR: 80, 90), life expectancy 3 yrs (IQR: 2, 4.8) or ECOG ≥ 2 (IQR: 2,3). Patients were considered ineligible for palliative chemotherapy at median age 90 (IQR: 80, 92.5), life expectancy ≤ 2 years (IQR: 1.5, 3) or ECOG status ≤ 3 (IQR: 3, 3). Patients with above average comorbidity were considered ineligible for salvage surgery at median age 80 yrs (IQR: 75, 80) and palliative chemotherapy at median age 80 yrs (IQR: 75, 85). 8 comorbidities were identified by > 75% of the respondents as determinants of treatment ineligibility. 12 respondents (60%) indicated follow-up of patients ineligible for treatment should be continued based on patient desire, ongoing management of late effects, and continuity of care. However, a majority (n = 15) responded that clinic visits only should be continued without further testing. Conclusions: Considerable agreement was observed regarding patient characteristics that lead to ineligibility for treatment of recurrent disease. This information can aid shared clinical decision-making for post-treatment surveillance strategies and may potentially reduce variation in surveillance practice.

107 Background: Pancreatobiliary carcinomas (PC) carry a poor prognosis but have not yet benefitted from the revolution in precision oncology, in part because biopsy tissue is often inadequate for ...

4107 Background: Resection of gastroenteropancreatic NETs is known to prolong survival. Current NCCN guidelines recommend that complete surgical resection of the primary tumor and metastases should...

2540 Background: Nesvacumab (N) is an Ang2 selective, human MAb that potently blocks signaling through the Tie2 receptor, inhibiting tumor angiogenesis and growth. In mouse xenograft models of huma...

4022 Background: Data from animal and cell line models suggest that vitamin D metabolism is important in pancreatic tumor maintenance and may contribute to this tumor’s chemoresistance. While vitamin D has been implicated in a variety of cancers, the prevalence of vitamin D deficiency among patients with advanced pancreatic cancer (APC) and the effect of baseline vitamin D levels on survival outcomes are unknown. Methods: CALGB 80303 was a randomized controlled trial of patients with APC which demonstrated no difference in OS among patients treated with gemcitabine (GEM) vs. GEM + bevacizumab. We retrospectively measured baseline serum 25(OH)D levels and examined associations between baseline 25(OH)D levels and selected patient characteristics. Using the Cox rank score test, we examined the association between 25(OH)D level and PFS and OS. The differences in the levels among racial populations were tested using the Kruskal-Wallis test. Results: Of 256 patients with available serum, the median 25(OH)D level was 21.7 (range 4–77). 44.5% of patients were vitamin D deficient (25(OH)D

239 Background: Phase III studies of B in unselected APCA pts have been negative. Recent data suggest subsets of pts may benefit from B, but no validated predictive biomarkers exist for B efficacy in APCA. The pathogenesis of B-related HTN (B-HTN) is not well understood, but studies suggest association between B-HTN and improved clinical outcome in various advanced solid tumors. We conducted a pooled analysis of raw data from 4 prospective clinical trials to evaluate that predictive role of B-HTN in APCA. Methods: Relevant raw data were collected from 4 multi-institution single-arm phase II trials of GEM-based doublet chemotherapy + B as 1st line treatment of APCA. Pts were grouped according to B-HTN of any grade (Group 1) and no B-HTN (Group 2). Clinical outcomes including OS, TTP, ORR, and DCR (disease control rate = ORR + SD >16 weeks) were compared between Group 1 and 2. For pts in Group 1, outcomes were also compared according to CTCAE HTN grade (1-2 vs 3-4). Results: 166 pts (85 M, 81 F) with median age 55 (31-85) were included. Group 1= 37 pts (Grade 1-2 HTN, N=18; Grade 3-4 HTN, N=19), Group 2 = 129 pts. Demographics were similar except % stage 4 (92% group 1, 100% group 2, p=0.01). Results are summarized in the Table. Group 1 had significantly prolonged mOS and mTTPand improved ORR and DCR vs Group 2. There was no difference in outcome according to HTN grade. Conclusions: B-HTN of any grade may be an important pharmacodynamic biomarker for B in APCA. This subset of pts could benefit from B and identification of characteristics that predict development of B-HTN may aid in future pt selection for B therapy in APCA. Future prospective studies may consider pharmacodynamic titration of B to grade > 1 HTN to potentially maximize B efficacy. [Table: see text]

4038 Background: GEM has served as the chemotherapy platform for most phase III clinical trials in APC, inc. CALGB 80303 (GEM +/- BEV). However, GEM-based combination regimens may confer superior outcomes in select pts and represent a preferred backbone in clinical trial design testing targeted agents. Methods: Data was pooled from 5 phase II trials evaluating GEM-based cytotoxic doublets plus BEV in APC. 1o endpoint was OS. 2o endpoints included ORR, CA19-9 response, and adverse events (AEs). Kaplan-Meier methods estimated time-to-event endpoints. The Cox proportional hazard model estimated univariate hazard ratios (HR) of death. Results: Of 261 pts, 90.7% were Caucasian, 95.4% had an ECOG PS 0-1, and 91.6% had metastatic disease. Median age = 60y. Pooled OS data (in mos), stratified for PS and stage, is shown in the table. ORR across all trials: CR 1.6%, PR 22.9%, SD 50.8%, PD 20.2%, NA 4.7%. HR for pts who achieved disease control (CR/PR/SD) was 0.35 vs. those with PD (95% CI 0.23-0.54, p