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PURPOSE With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone. METHODS We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration–approved label, and consideration of additional or orthogonal molecular testing. RESULTS We reviewed genomic data and provided clinical recommendations for 506 patients with GI cancer who underwent tumor molecular profiling between January and June 2019 and determined follow-up using the electronic health record. Summary reports were provided to 19 medical oncologists for patients with colorectal (n = 198, 39%), pancreatic (n = 124, 24%), esophagogastric (n = 67, 13%), biliary (n = 40, 8%), and other GI cancers. We recommended ≥ 1 precision medicine clinical trial for 80% (406 of 506) of patients, leading to 24 enrollments. We recommended on-label and off-label targeted therapies for 6% (28 of 506) and 25% (125 of 506) of patients, respectively. Recommendations for additional or orthogonal testing were made for 42% (211 of 506) of patients. CONCLUSION The integration of precision medicine in routine cancer care through a dedicated multidisciplinary molecular tumor board is scalable and sustainable, and implementation of precision oncology recommendations has clinical utility for patients with cancer.

Background Trifluridine/tipiracil (FTD/TPI) and regorafenib prolong survival for patients with refractory metastatic colorectal cancer (mCRC); limited comparative effectiveness data exist. Materials and Methods A retrospective, longitudinal cohort study of patients with mCRC who initiated FTD/TPI or regorafenib (index therapy) between 2012 and 2017 at a U.S. tertiary oncology center, Dana-Farber Cancer Institute, was conducted. Using best tumor response assessments, real-world overall response rates (rwORR) and disease control rates (rwDCR) were described and analyzed using logistic regression. Survival rate was examined for each month after index therapy using Kaplan-Meier. Overall survival (OS) was assessed using Cox proportional hazards models. Subgroup analyses among patients with index therapy as second- or third-line were performed. Results One hundred twenty-six and 95 patients were treated with FTD/TPI or regorafenib as index therapy, respectively. Patients treated with FTD/TPI versus regorafenib had a better response (rwORR 52.5% vs. 34.2%; adjusted odds ratio [OR] = 2.6; all p value Conclusion Patients treated with FTD/TPI had better tumor response and disease control than patients treated with regorafenib. Subgroup analysis in second- or third-line suggests that early use of FTD/TPI may have clinical benefits. Implications for Practice In this retrospective cohort study, patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil (FTD/TPI) were significantly less likely than those treated with regorafenib to have dose modifications and more likely to have higher real-world objective response rate (rwORR) and real-world disease control rate (rwDCR) while treated. Patients treated with FTD/TPI versus regorafenib had significantly higher odds of having rwORR or rwDCR in adjusted analyses. Monthly survival rates were higher overall in patients treated with FTD/TPI versus regorafenib in the first 6 months of follow-up, particularly at months 3 and 4. This study offers insight into patients' treatment experience in real-world clinical settings.

We conducted next-generation DNA sequencing on 335 biliary tract cancers and characterized the genomic landscape by anatomic site within the biliary tree. In addition to frequent FGFR2 fusions among patients with intrahepatic cholangiocarcinoma (IHCC), we identified FGFR2 extracellular domain in-frame deletions (EID) in 5 of 178 (2.8%) patients with IHCC, including two patients with FGFR2 p.H167_N173del. Expression of this FGFR2 EID in NIH3T3 cells resulted in constitutive FGFR2 activation, oncogenic transformation, and sensitivity to FGFR inhibitors. Three patients with FGFR2 EIDs were treated with Debio 1347, an oral FGFR1/2/3 inhibitor, and all showed partial responses. One patient developed an acquired L618F FGFR2 kinase domain mutation at disease progression and experienced a further partial response for 17 months to an irreversible FGFR2 inhibitor, futibatinib. Together, these findings reveal FGFR2 EIDs as an alternative mechanism of FGFR2 activation in IHCC that predicts sensitivity to FGFR inhibitors in the clinic.Significance:FGFR2 EIDs are transforming genomic alterations that occur predominantly in patients with IHCC. These FGFR2 EIDs are sensitive to FGFR inhibition in vitro, and patients with these alterations benefited from treatment with FGFR inhibitors in the clinic.This article is highlighted in the In This Issue feature, p. 2355

Background Trifluridine and tipiracil (FTD + TPI) and regorafenib (REG) are approved treatments for the treatment of refractory metastatic colorectal cancer (mCRC). This study assesses adherence and duration of therapy with FTD + TPI versus REG and explores the effect of sequencing on adherence. Materials and Methods Adults diagnosed with mCRC were identified in the IQVIA Real‐World Data Adjudicated Claims: U.S. database (October 2014–July 2017). The observation period spanned from the index date (first dispensing of FTD + TPI or REG) to the earliest of a switch to another mCRC agent, the end of continuous enrollment, or the end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC), and persistence and time to discontinuation (gap ≥45 days) were compared between FTD + TPI and REG users and among switchers (FTD + TPI‐to‐REG vs. REG‐to‐FTD + TPI). Results A total of 469 FTD + TPI and 311 REG users were identified. FTD + TPI users had higher compliance with an MPR ≥80% (odds ratio [OR], 2.47; p < .001) and PDC ≥80% (OR, 2.77; p < .001). FTD + TPI users had better persistence (82.8% vs. 68.0%; p < .001) and lower risk of discontinuation (hazard ratio [HR], 0.76; p = .006). Among switchers (96 FTD + TPI‐to‐REG; 83 REG‐to‐FTD + TPI), those switching from FTD + TPI to REG were more likely to have an MPR ≥80% (OR, 2.91; p < .001) and PDC ≥80% (OR, 4.60; p < .001) compared with REG‐to‐FTD + TPI switchers while treated with these drugs. Additionally, FTD + TPI‐to‐REG switchers had a lower risk of first treatment discontinuation (HR, 0.66; p = .009). Conclusion FTD + TPI users had significantly higher adherence and persistence, and patients who were treated with FTD + TPI before switching to REG also had higher adherence and persistence outcomes. Implications for Practice Trifluridine plus tipiracil (FTD + TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) but have different tolerability profiles. This study assessed real‐world adherence to treatment with FTD + TPI versus REG and compared outcomes among patients who switched from FTD + TPI to REG and vice versa. FTD + TPI was associated with significantly higher medication adherence and longer time to discontinuation than REG. Patients treated with FTD + TPI prior to switching to REG also showed higher adherence outcomes. Findings could help inform decision making regarding the choice and sequencing of treatment with FTD + TPI versus REG in patients with mCRC., This article assesses real‐world treatment patterns and adherence of patients with metastatic colorectal cancer treated with trifluridine plus tipiracil (FTD/TPI) versus regorafenib (REG) and explores the effect of the treatment sequence on adherence among patients who switched from FTD + TPI to REG and vice versa.

BackgroundImmune checkpoint inhibitors have revolutionized cancer treatment, but the benefits in refractory patients with esophageal cancer have been modest. Predictors of response as well as new targets for novel therapeutic combinations are needed. In this phase 2 clinical trial, we tested single-agent pembrolizumab in patients with advanced esophageal cancer, who received at least one prior line of therapy.MethodsPembrolizumab 200 mg every 3 weeks was tested in 49 patients with refractory esophageal cancer: 39 with adenocarcinoma and 10 with esophageal squamous cell carcinoma. Major endpoints were radiological response by Immune-related Response Evaluation Criteria In Solid Tumors and survival. Tumor samples were evaluated for programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and immune contexture by both NanoString mRNA expression analysis and flow cytometry. Peripheral blood mononuclear cells and a panel of circulating chemokines were also analyzed.ResultsThe overall response rate (ORR) was 8% (4 of 49 patients; 95% CI 2.3% to 19.6%). Median overall survival (OS) was 5.8 months (95% CI 4.0 to 9.5). ORR and OS were not associated with histology. For PD-L1-positive patients, ORR was 13.3% (95% CI 1.7% to 40.5%) and median OS was 7.9 months (95% CI 4.7 to 15.5). A trend toward improved OS was observed in seven patients with a TMB ≥10 mut/Mb (p=0.086). Tumors with a PD-L1 Combined Positive Score ≥1 showed enrichment of LAG3 (p=0.005) and IDO1 (p=0.04) gene expression. Baseline levels of circulating CXCL10, interleukin 2 (IL2) receptor α (IL2RA) and IL6 were associated with survival: CXCL10 favorably, (HR 0.37, p=0.002 (progression-free survival); HR 0.55, p=0.018 (OS)); IL2RA and IL6 unfavorably (HR 1.57, p=0.020 for IL6 (OS); HR 2.36, p=0.025 for IL2RA (OS)).ConclusionsPembrolizumab monotherapy was modestly effective in refractory esophageal cancer. Circulating CXCL10 at baseline appeared to be a robust predictor of response. Other T cell exhaustion markers are upregulated in PD-L1-positive patients, suggesting that immunotherapy combinations such as anti-LAG3/programmed cell death protein 1 (PD-1) or anti-IDO1/PD-1 may be of promise in refractory esophageal cancer.

BACKGROUND: MEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition. METHODS: This open-label phase II study randomized patients with BTC to atezolizumab (anti–PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS). RESULTS: Seventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a median PFS of 3.65 months in the combination arm versus 1.87 months in the monotherapy arm (HR 0.58, 90% CI 0.35–0.93, 1-tail P = 0.027). One patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%) had a partial response. Combination therapy was associated with more rash, gastrointestinal events, CPK elevations, and thrombocytopenia. Exploratory analysis of tumor biopsies revealed enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios with combination treatment. Patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells had evidence of greater clinical benefit from the combination. CONCLUSION: The combination of atezolizumab plus cobimetinib prolonged PFS as compared with atezolizumab monotherapy, but the low response rate in both arms highlights the immune-resistant nature of BTCs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201458. FUNDING: National Cancer Institute (NCI) Experimental Therapeutics Clinical Trials Network (ETCTN); F. Hoffmann-La Roche, Ltd.; NCI, NIH (R01 CA228414-01 and UM1CA186691); NCI’s Specialized Program of Research Excellence (SPORE) in Gastrointestinal Cancers (P50 CA062924); NIH Center Core Grant (P30 CA006973); and the Passano Foundation.

Biliary tract cancers are rare, aggressive neoplasms. Most patients present with advanced/unresectable or metastatic disease at diagnosis, and no second-line regimen has demonstrated clinical benefit. This was a phase 2 study evaluating the efficacy and safety of regorafenib in patients who had advanced/unresectable or metastatic disease after receiving standard therapy.In this single arm-study, patients with advanced/unresectable or metastatic biliary tract cancer who failed at least 1 line of systemic chemotherapy received regorafenib once daily on a schedule of 21-days on/7-days off in a 28-day cycle. Patients initially received a standard 160 mg dose. After toxicity assessments in the first 3 patients, the dose was reduced to 120 mg for subsequent patients, as preplanned. The primary endpoint was progression-free survival (PFS). Secondary objectives included overall survival (OS), the objective response rate, and the disease control rate.Forty-three patients received at least 1 dose of regorafenib, and 34 patients who received at least 1 cycle of treatment were evaluable for tumor response. The median PFS was 15.6 weeks (90% confidence interval, 12.9-24.7 weeks), and the median OS was 31.8 weeks (90% confidence interval, 13.3-74.3 weeks), with survival rates 40% at 12 months and 32% at 18 months. A partial response was achieved in 5 patients (11%), and 19 had stable disease (44%), for a disease control rate of 56%. The toxicity profile was as expected, with grade 3 and 4 adverse events reported in 40% of patients. The most common toxicities were hypophosphatemia (40%), hyperbilirubinemia (26%), hypertension (23%), and hand-foot skin reaction (7%).The current results suggest promising efficacy of regorafenib in patients with chemotherapy-refractory, advanced/metastatic biliary tract cancer, warranting further studies to confirm its clinical efficacy. There is a clear unmet need for effective therapies in patients who have advanced and metastatic biliary tract cancer.

Clinically relevant subtypes exist for pancreatic ductal adenocarcinoma (PDAC), but molecular characterization is not yet standard in clinical care. We implemented a biopsy protocol to perform time-sensitive whole-exome sequencing and RNA sequencing for patients with advanced PDAC. Therapeutically relevant genomic alterations were identified in 48% (34/71) and pathogenic/likely pathogenic germline alterations in 18% (13/71) of patients. Overall, 30% (21/71) of enrolled patients experienced a change in clinical management as a result of genomic data. Twenty-six patients had germline and/or somatic alterations in DNA-damage repair genes, and 5 additional patients had mutational signatures of homologous recombination deficiency but no identified causal genomic alteration. Two patients had oncogenic in-frame BRAF deletions, and we report the first clinical evidence that this alteration confers sensitivity to MAPK pathway inhibition. Moreover, we identified tumor/stroma gene expression signatures with clinical relevance. Collectively, these data demonstrate the feasibility and value of real-time genomic characterization of advanced PDAC. Significance: Molecular analyses of metastatic PDAC tumors are challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. Using an integrated multidisciplinary biopsy program, we demonstrate that real-time genomic characterization of advanced PDAC can identify clinically relevant alterations that inform management of this difficult disease. Cancer Discov; 8(9); 1096–111. ©2018 AACR. See related commentary by Collisson, p. 1062. This article is highlighted in the In This Issue feature, p. 1047

Trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) prolong survival in refractory metastatic colorectal cancer (mCRC) and have similar indications with different side-effect profiles. The present study compared real-world treatment patterns with FTD/TPI and REG for mCRC in a large, representative US claims database.Retrospective data from the US Symphony Health Solutions' Integrated Dataverse database were analyzed for adult mCRC patients receiving FTD/TPI or REG from October 2014 to July 2016. The index date was the first FTD/TPI or REG prescription date. The observation period spanned from the index date to the end of data collection, end of continuous clinical activity, or treatment switch. Adherence was assessed using the medication possession ratio and proportion of days covered at 3 months. The time to discontinuation was assessed over the observation period with gaps of 45, 60, or 90 days. Outcomes were compared between the cohorts using logistic regression and Cox proportional hazards models adjusting for baseline characteristic differences.A total of 1630 FTD/TPI patients and 1425 REG patients were identified. The FTD/TPI patients were 80% more likely to have a medication possession ratio of ≥ 0.80 compared with the REG patients (odds ratio, 1.80; P .001) and more than twice as likely to have a proportion of days covered of ≥ 0.80 (odds ratio, 2.66; P .001) at 3 months. The FTD/TPI patients were 37% less likely to discontinue their treatment compared with the REG patients when using the 60-day gap (hazard ratio, 0.63; P .001). Similar results were found using the 45- and 90-day gaps.mCRC patients taking FTD/TPI were significantly more likely to adhere to and comply with therapy compared with those taking REG.

e18834 Background: A growing number of genomic alterations inform treatment of advanced/metastatic colorectal cancer (mCRC). However, use of comprehensive genomic profiling (CGP) is limited in the first-line (1L) setting. Based on the Tempus xT next-generation sequencing assay, we estimated the impact of expanded 1L CGP on the detection of currently actionable alterations in mCRC and associated diagnostic testing costs in a modeled US health plan setting. Methods: A decision analytic model was used to compare testing scenarios over a two-year time horizon: current 1L testing with a mix of CGP and non-CGP diagnostics vs. replacing 20% of usual testing with Tempus CGP. The incidence of 1L mCRC, current testing rates, prevalence of actionable alterations, and test sensitivity were drawn from a literature review and clinical expert input. Currently actionable alterations included KRAS, NRAS, RAF, BRAF, dMMR/MSI, NTRK, RET, EGFR, HER2, MET, PIK3CA and POLE1. Cost components included initial and repeat testing, physician-associated and administrative costs. Opportunities for genomically-informed therapy or clinical trials were assessed under each testing scenario. A forward looking scenario, with additional informative alterations, was also explored. Results: In a hypothetical five million-member health plan, with 50% Medicare and 50% commercial insurance, 1,112 incident cases of mCRC (22 per 100,000 patients) are expected in a typical year. Among these cases, 566 (51%) are expected to undergo 1L molecular diagnostic testing, with 55 projected to undergo repeat testing upon progression within the next year. Based on current real-world testing rates, there are an expected 521 missed opportunities for genomically informed treatment (47% of the incident mCRC population), with 442 missed due to lack of testing and 79 due to testing without CGP. Replacing 20% of usual testing with Tempus CGP in the modeled scenario was associated with up to a $0.003 per member per month (PMPM) testing cost increase and an additional 15.5 patients with an opportunity for genomically-informed care (12.7 patients for guideline-recommended treatment and 2.8 for a clinical trial). The number needed to test (NNT) with Tempus CGP versus the usual mix of testing was 7.8 1L patients to identify one actionable alteration. Scenario analyses projecting the advent of additional genomically-informed treatments and clinical trials resulted in smaller numbers needed to test. Conclusions: Replacing 20% of usual testing with Tempus CGP is associated with a small incremental testing cost but can identify actionable alterations for a meaningful number of patients. For every eight 1L mCRC patients tested with Tempus CGP rather than the usual mix of molecular testing, one additional patient is expected to be identified as having currently actionable alterations.

Background: BTCs are aggressive cancers with a poor prognosis. In preclinical models, MEK inhibition modulates the tumor immune microenvironment and enhances responses to programmed death-ligand 1 (PD-L1) inhibition. We report a randomized, open-label, multicenter phase 2 trial of atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor) in BTC (NCT03201458). Methods: Eligible patients had advanced BTC [intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC)], with 1-2 lines of prior therapy in the metastatic setting, measurable disease by RECIST v1.1, and ECOG performance status ≤1. Patients randomized to Arm A received atezolizumab 840 mg IV Q2w. Patients randomized to Arm B received oral cobimetinib 60 mg daily (21 days on/7 days off) plus atezolizumab 840 mg IV Q2w. The primary endpoint was progression free survival (PFS) using the Kaplan-Meier method and compared between groups under the assumption of Cox proportional hazards, stratified for primary tumor site. Secondary endpoints included objective response rate (ORR), safety and tolerability, and overall survival (OS). Results: 86 patients were enrolled at 23 centers in the United States; 77 patients were randomized and received at least one dose of study therapy (Arm A: n=37, ICC=21, ECC=7, GBC=11; Arm B: n=38, ICC=22, ECC=8, GBC=8). Median age was 63 (range 44-86), and 48 (62%) were female. The trial met its primary endpoint, with a median PFS of 3.65 months (cobimetinib+atezolizumab) vs 1.87 months (atezolizumab monotherapy) (p=0.027). OS data are not mature at the time of analysis. There was 1 PR (3.2%), 13 SD (41.9%), and 17 PD (54.8%) in the combination arm and 1 PR (2.9%), 10 SD (29.4%), and 23 PD (67.6%) in the atezolizumab monotherapy arm. Two patients in the combination arm remain on therapy 15+ months from enrollment. One patient in each treatment arm had known mismatch repair deficiency (MMRd), of whom 1 had PD as a best response and the other withdrew prior to response evaluation. Grade 3-4 treatment-related adverse events were similar in both arms, and there were no treatment-related deaths. 4 (10%) of patients receiving atezolizumab monotherapy and 8 (22.2%) receiving cobimetinib+atezolizumab discontinued therapy due to adverse events. Changes in tumor CD8, CD4, FoxP3, PDL1, and MHC expression from paired tumor biopsies will be presented at the conference. Conclusions: We report the first randomized trial of immunotherapy in BTC. The combination of atezolizumab plus cobimetinib met its primary endpoint and significantly prolonged PFS as compared to atezolizumab monotherapy in BTC. The combination of atezolizumab and cobimetinib had manageable toxicity and warrants further investigation in BTC. Citation Format: Mark Yarchoan, Leslie Cope, Robert A. Anders, Anne Noonan, Laura W. Goff, Lipika Goyal, Jill Lacy, Daneng Li, Anuj Patel, Aiwu R. He, Ghassan Abou-Alfa, Kristen Spencer, Edward Kim, Stephanie Xavier, Amanda Ruggieri, S. Lindsey Davis, Autumn McRee, Paul Kunk, Qingfeng Zhu, Andrea Wang-Gillam, Andrew Poklepovic, Helen Chen, Elad Sharon, Gregory B. Lesinski, Nilo Azad. A multicenter randomized phase 2 trial of atezolizumab as monotherapy or in combination with cobimetinib in biliary tract cancers (BTCs): A NCI Experimental Therapeutics Clinical Trials Network (ETCTN) study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT043.

567 Background: Fibroblast growth factor receptor (FGFR) pathway alterations have been identified in approximately 20% of patients (pts) with intrahepatic cholangiocarcinoma (IHCC), most commonly by FGFR2 fusions. Early phase clinical trials have demonstrated encouraging efficacy of FGFR inhibitors in pts with FGFR2-translocated cholangiocarcinoma, but efficacy in pts with other FGFR2 activating alterations is less clear. Methods: Pts with cholangiocarcinoma underwent CLIA-certified next generation DNA sequencing (NGS) to identify actionable alterations. FGFR2 fusions and other FGFR2 genomic events were assessed, with genomic characterization performed before and after treatment with FGFR inhibitors in appropriate pts. Novel extracellular domain in-frame deletions (INDELs) of FGFR2 and apparent resistance mutations were investigated for oncogenic activity and inhibitor resistance in vitro and in vivo. Results: Cholangiocarcinomas from 284 pts (136 male, 148 female; median age, 64 [20-89], including 139 IHCCs, were sequenced. Among the IHCCs, 16 (11.5%) had FGFR2 fusions, with 9 different gene partners. Surprisingly, 5 (3.6%) IHCCs harbored extracellular domain FGFR2 INDELs. Two of these IHCCs harbored an exon 5 deletion FGFR2 p.H167_N173del. Expression of FGFR2 p.H167_N173del in 3T3 cells resulted in oncogenic transformation. In the clinic, two pts with FGFR2 p.H167_N173del were treated with Debio1347, an oral FGFR-1/2/3 inhibitor. Both patients achieved a durable partial response (PR) of 11 months, with one of the pts still on active treatment with Debio-1347. The patient who developed acquired resistance underwent repeat biopsy, and NGS identified a secondary mutation ( FGFR2 p. L617F) in the kinase domain. In vitro studies demonstrated that this mutation confers resistance to Debio1347. This patient was subsequently treated with another FGFR inhibitor and again experienced a PR lasting 17 months. A third biopsy after disease progression demonstrated a previously undetected L597Q BRAF mutation. Conclusions: Extracellular domain FGFR2 in-frame deletions are a novel genomic alteration in IHCC that are transforming and predict clinical sensitivity to FGFR inhibitors.

77 Background: There is an increased use of oral anti-cancer therapies (OACTs) for treatment of gastrointestinal (GI) cancers. While OACTs provide convenience compared to IV agents, they carry similar risks for drug-drug interactions (DDI), toxicities, and unique challenges like adherence and drug access. Patients on OACTs have fewer touch-points with clinicians, requiring more patient ownership of treatment. Pharmacist co-management of pts has been shown to be successful in teaching and monitoring of IV therapy. We sought to assess feasibility of pharmacist co-management for pts prescribed OACTs for treatment of GI cancers. Methods: In 2019, the Dana-Farber GI Cancer Center (GCC) had an embedded pharmacist 8 hrs/week to help with co-management of pts on OACTs. The pharmacist provided (1) in-person and telephone teaching; (2) comprehensive medication reconciliation; (3) DDI review; and (4) supportive care recommendations. Patients were identified by reviewing provider schedules and through provider referrals. The initial teach visit was one-on-one with each patient before initiation, with joint visits with providers thereafter for monitoring and adherence checks. Data were collected to quantify the types of support/recommendation provided by pharmacist and the impact on clinical workflow. Results: After 4 months in the GCC clinic, the pharmacist has co-managed 26 new pts, 61% seen in-person. In initial visits, the pharmacist identified 3 DDI, updated 15 medication lists, and assisted 11 pts/or providers with drug access and drug information. The pharmacist saw 10 of 26 pts for follow up, totaling 21 encounters. The pharmacist assisted in 17 of the 21 encounters with drug access and drug information. Pharmacist spent 20 min/pt on teaching. For follow-up visits, the pharmacist did not additional incur clinic resources as patients were seen with providers. Conclusions: Pharmacist co-management of patients on OACTs is feasible and offers an added safety resource to pts and providers from initial teaching to monitoring. Future research will focus on the impacts of co-management on clinical outcomes, such as the use of emergency/hospital visits, the duration of therapy, and adherence.

592 Background: FTD/TPI and REG have both demonstrated prolonged survival in refractory mCRC patients (pts) when compared to placebo but limited comparative effectiveness data are available. This study aims to compare outcomes following initiation of FTD/TPI or REG for mCRC at a single academic cancer center. Methods: Retrospective chart reviews were conducted in all pts with mCRC who initiated FTD/TPI or REG between 2012-2017. Analyses of time from index therapy initiation to discontinuation for any reason (TTD), real-world response rates (rwRR) and disease control rates (rwDCR) were performed. Cox proportional hazards models adjusting for demographic and clinical characteristics were performed for overall survival (OS). Results: 126 FTD/TPI and 95 REG pts were included. Baseline characteristics were similar in both groups, though more pts treated with FTD/TPI had right-sided primary tumors compared to REG (30.4% vs. 25.5%, p = 0.43). Treatment patterns pre- and post-index therapy were comparable in both groups. Median observation duration for FTD/TPI and REG was 7.1 and 6.3 months, respectively. Mean TTD was 88.4 days for FTD/TPI pts and 84.2 days for REG pts (p = 0.42). Fewer pts treated with FTD/TPI discontinued due to toxicities than pts treated with REG (8.2% vs. 24.2%, p = 0.001). A higher proportion of FTD/TPI pts had no dose modifications vs. REG pts (84.0% vs. 64.1%, p < 0.001). OS was similar between the two groups (adjusted hazard ratio [HR] FTD/TPI vs. REG: 0.79, p = 0.13). FTD/TPI pts had higher rwRR (52.5% vs. 34.2%, p = 0.01) and rwDCR (64.2% vs. 46.1%, p = 0.01) than REG pts. In the subgroup of pts ≥ 65 years, mean TTD was higher in FTD/TPI pts (105.9 vs. 77.6 days, p = 0.004). Pts ≥ 65 years receiving FTD/TPI had better OS than REG pts (HR: 0.51, p = 0.03). Conclusions: In this single institution study, TTD and OS were similar between pts treated with FTD/TPI and REG. Fewer pts treated with FTD/TPI than REG discontinued due to toxicities or required dose modification. Reported responses rates were higher in FTD/TPI pts. Older pts (≥ 65 years) on FTD/TPI remained on treatment longer and had better OS than REG pts.

11 Background: Adherence to oral chemotherapies is a critical but difficult to measure factor in the care of patients with advanced cancer. FTD/TPI and REG have both demonstrated prolonged survival in patients with refractory mCRC, but with notably different side effect profiles. This study utilizes real-world data to assess adherence and discontinuation of patients treated with FTD/TPI or REG and explore the effect of sequencing on adherence. Methods: Adults diagnosed with mCRC were identified using the nationally representative IQVIA Real-World Data Adjudicated Claims – US database (10/2014–07/2017). The first dispensing date of FTD/TPI or REG (if after FTD/TPI approval [10/2015]) was defined as the index date and the 3 months before as the baseline period. The observation period spanned from the index to the earliest date of a switch to another mCRC agent, end of continuous enrollment, or end of data availability. Medication possession ratio (MPR), proportion of days covered (PDC) at 3 months, and discontinuation (i.e., allowable gap≥45 days) were compared. Logistic (odds ratio [OR]) and Cox proportional hazards (hazard ratio [HR]) regressions, adjusting for baseline characteristics, were used to compare adherence and discontinuation, respectively. A subgroup analysis was conducted among switchers (FTD/TPI to REG vs REG to FTD/TPI). Results: A total of 469 FTD/TPI and 311 REG users were identified. FTD/TPI users had higher compliance with an MPR ≥ 80% (OR = 2.47; p < 0.001) and PDC ≥ 80% (OR = 2.77; p < 0.001). FTD/TPI users had lower risk of discontinuation (HR = 0.76; p = 0.006). Among switchers (96 FTD/TPI to REG; 83 REG to FTD/TPI), those switching from FTD/TPI to REG were more likely to have an MPR ≥ 80% (OR = 2.91; p < 0.001) and PDC ≥ 80% (OR = 4.60; p < 0.001) compared to REG to FTD/TPI switchers. Additionally, FTD/TPI to REG switchers had a lower risk of first treatment discontinuation (HR = 0.66; p = 0.009). Conclusions: In this study, FTD/TPI users had significantly higher compliance, lower discontinuation rate, and switchers treated first with FTD/TPI had better compliance, demonstrating that claims data can provide insight into oral chemotherapy adherence patterns in mCRC.

e16072Background: There are limited treatment (tx) options for metastatic esophageal cancer patients (pts). We sought to determine the safety and efficacy of pembro among US pts with previously tre...

666 Background: FTD/TPI and REG both prolong survival in refractory mCRC and have similar indications with different side effect profiles. This study compares real-world treatment patterns with FTD/TPI and REG for mCRC in a large, representative US claims database. Methods: Retrospective data from 10/2014 to 7/2016 from the US Symphony Health Solutions’ Integrated Dataverse (IDV®) database were analyzed for patients receiving FTD/TPI or REG. The index date was the date of first FTD/TPI or REG prescription. Patients were included if: 1) age ≥18 years old, 2) ≥1 CRC diagnosis, 3) no diagnosis of gastric cancer or gastrointestinal stromal tumor, and 4) continuous clinical activity for ≥3 months before and after index date. The observation period spanned from index date to end of data, end of continuous clinical activity, or switch to another mCRC treatment. Adherence was assessed using medication possession ratio (MPR) ≥0.80 and proportion of days covered (PDC) ≥0.80 at 3 months. Compliance was assessed using time to discontinuation over the observation period using allowable gaps of 45, 60, or 90 days. Patients who never discontinued therapy were censored at the end of the observation period. Outcomes were compared between FTD/TPI and REG using multivariate logistic regression and Cox proportional hazards models, adjusting for demographic and clinical baseline characteristics. Results: A total of 1,630 FTD/TPI patients and 1,425 REG patients were identified. Mean ± standard deviation (SD) age of FTD/TPI patients was 61.0 ± 11.0 compared to 62.8 ± 10.9 for REG patients (p < 0.001). FTD/TPI patients were 80% more likely to have a MPR ≥0.80 compared to those on REG (Odds Ratio [OR] = 1.80, p < 0.001) and more than twice as likely to have a PDC ≥0.80 (OR = 2.66, p < 0.001) at 3 months. FTD/TPI patients were 37% less likely to discontinue their treatment compared to those on REG when using gaps of 60 days (Hazard Ratio = 0.63, p < 0.001). Similar results were found with 45 and 90 days. Conclusions: In this retrospective study of mCRC patients, patients on FTD/TPI were significantly more likely to adhere and comply with therapy compared to those on REG.

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth-leading cause of cancer-related death in the United States and is projected to become the second leading cause by 2030. Most patients present with advanced disease and die within 12 months of diagnosis. Recent genomic studies of primary pancreatic cancer resection specimens have identified several molecular alterations and genomic subtypes of the disease that may guide precision medicine approaches to clinical management. However, the molecular landscape of metastatic PDAC has been less well characterized. Moreover, biopsy-driven studies in metastatic PDAC have been historically very challenging due to the aggressive course of this disease as well as the low-volume and heterogeneous nature of biopsies that makes deep molecular characterization difficult. Insufficient genomic analysis of a patient’s tumor early in their disease course is a major barrier to enrollment on clinical trials of targeted therapies. To address these limitations, we have implemented a multi-disciplinary clinical and research biopsy protocol to enable real time comprehensive molecular characterization of metastatic PDAC biopsy specimens. We have performed core needle biopsies of metastatic lesions in the liver or peritoneal cavity in 42 patients at the time of initial presentation. A low rate of complications was observed, with only a single patient having a self-limited hemorrhagic complication after liver biopsy. On average, 4-6 separate biopsy specimens were collected from each patient for histopathology and genomic analysis. Whole exome sequencing (WES) was performed in a CLIA-certified laboratory and a comprehensive molecular report of somatic alterations and selected pathogenic germline variants was returned to the referring clinician with a typical turn-around time of 3-5 weeks. We observed a striking incidence of recurrent germline and somatic alterations in DNA-damage repair genes, such as BRCA2, ATM and CHEK2. We also observed alterations in genes with known therapeutic implications, such as BRAF, RNF43, STK11 and ROS, and in select cases, these results guided choice of second or third line therapy. In parallel to WES, we performed RNA sequencing on bulk tumor tissue and readily identified expression signatures defining multiple subtypes of tumor and stroma that may have prognostic or therapeutic implications for tumor- or stroma-directed therapies. Collectively, these results demonstrate the feasibility and value of real-time genomic characterization of metastatic PDAC and provide a path forward for improved stratification and enrollment of PDAC patients on molecularly defined clinical trials. Citation Format: Andrew J. Aguirre, Scott Carter, Nicholas Camarda, Arezou Ghazani, Jonathan Nowak, Annacarolina Da Silva, Lauren Brais, Dorisanne Ragon, Devin McCabe, Lori Marini, Kristin Anderka, Karla Helvie, Nelly Oliver, Ana Babic, Paul Shyn, Douglas Rubinson, Anuj Patel, James Cleary, Nadine McCleary, Matthew Kulke, Thomas Clancy, Leona Doyle, Jason Hornick, Christine Ardito-Abraham, Ruth Yu, Michael Downes, Ronald Evans, Richard A. Moffitt, Jen Jen Yeh, William C. Hahn, Charles Fuchs, Robert Mayer, Nikhil Wagle, David Tuveson, Levi A. Garraway, Brian M. Wolpin. Real-time genomic characterization of metastatic pancreatic cancer to enable precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3036. doi:10.1158/1538-7445.AM2017-3036

e15000 Background: FTD-TPI and REG both prolong survival in refractory mCRC. Both agents have the benefit of oral administration but with distinct side effect profiles. This study aims to compare real-world treatment patterns following initiation of FTD-TPI or REG for mCRC in a large, nationally representative US claims database. Methods: Retrospective data from 10/2014 to 7/2016 from the US Symphony Health Solutions’ Integrated Dataverse (IDV®) database were analyzed for patients (pts) receiving FTD-TPI or REG. The index date was the date of first FTD-TPI or REG prescription. Pts were included if: 1) age ≥18 years old, 2) ≥1 CRC diagnosis, 3) no diagnosis of gastric cancer or gastrointestinal stromal tumor, and 4) continuous clinical activity for ≥3 months before and after index date. The observation period spanned from index date to end of data, end of continuous clinical activity, or switch to another mCRC treatment. Medication adherence was assessed by medication possession ratio (MPR), with MPR ≥80% as the defined threshold for adherence, as well as by proportion of days covered (PDC) at 3 months. Between treatment groups, binary endpoints were compared using Chi-square tests and mean and median time to treatment discontinuation (TTD) were compared using t-test and Wilcoxon test, respectively. Results: The study population consisted of 1,630 FTD-TPI pts and 1,425 REG pts. Mean ± standard deviation (SD) age of FTD-TPI pts was 61 ± 11 and REG pts was 63 ± 11 (p < 0.01). Mean ± SD length of observation period in days was 161 ± 59 for FTD-TPI pts and REG pts was 212 ± 113 (p < 0.01). 84% of FTD-TPI and 74% of REG pts reached MPR ≥80% (p < 0.01). FTD-TPI pts had higher mean PDC (71% vs 59%, p < 0.01) than REG pts. Mean and median TTD were significantly longer for FTD-TPI than REG pts (mean: 101 vs. 88 days, p < 0.01; median: 97 vs. 69 days, p < 0.01). Conclusions: In this analysis of real-world medication utilization for mCRC pts, those pts started on FTD-TPI had significantly higher medication adherence and longer TTD than those on REG.

4081 Background: Biliary adenocarcinoma/cholangiocarcinoma is a rare but aggressive neoplasm. Most patients present with unresectable or metastatic disease with 5-year survival rate ~5%. No second-line regimen has demonstrated clinical benefit in this disease. Regorafenib is an oral multi-kinase inhibitor with potent antitumor activity. This single arm phase II study evaluates the efficacy and safety of regorafenib as a single agent in advanced or metastatic biliary carcinoma/cholangiocarcinoma pts who failed systemic chemotherapy. Methods: Patients with ECOG PS 0-1and adequate liver, kidney and bone marrow function were given regorafenib orally once daily, 21 days on and 7 days off in a 28-day cycle. The initial dose of 160 mg was given to the first 3 patients. After toxicity assessment, the dose was reduced to 120 mg for the subsequent pts. The primary endpoint is PFS with the null hypotheses of 2.0 months, and median PFS ≥3.5 months as evidence of the study drug activity (α = 0.10, 80% power). Secondary objectives include OS, RR, and DCR. Results: Thirty-seven patients received at least one dose of regorafenib, of whom 28 were evaluable for efficacy. All had previous gemcitabine/cisplatin treatment. The mean age was 62.5 (34.5-82.8) with 17 (46%) females. PR was achieved in 3 (10.7%), SD in 18 (64.3%, with DCR of 75%), and PD in 7 (25%). For all 37 patients, median PFS was 3.55 months (95% CI = 2.1- 5.72) and mOS was 5.55 months (95% CI = 4.04 -NA) with survival rate of 42 % at 12 months, and 38% at 18 months. Medan PFS and OS of 30 patients who had ≥1 cycle were 3.91 months (95% CI = 3.55-9.79) and 13.4 months (95% CI = 5.06 - NA), respectively. The overall toxicity profile was as expected, with G3/4 AE’s of 40.5%. The most common toxicities were HTN, hypophosphatemia, hand-foot skin reaction, and increased serum bilirubin. Dose modification was required in 11 (30.6%) patients. Tumor samples were collected in 80% of patients, with planned correlative studies underway. Conclusions: This study showed promising efficacy of regorafenib in chemotherapy refractory advanced/metastatic cholangiocarcinoma. Further studies to confirm the clinic efficacy are recommended. Clinical trial information: NCT02053376.