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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.

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.

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.