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PURPOSE Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes. METHODS Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel–related toxicity. RESULTS A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell–associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion ( P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached ( P < .0001) and 19 months versus not reached ( P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed ( P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion. CONCLUSION Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.

7552 Background: Axicabtagene Ciloleucel (Axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Long‐term analysis of the Zuma‐1 clinical trial showed ~40% of patients remained progression-free at 2 years (Locke, Lancet Oncology 2018). Early identification of patients who will later progress after CAR T cell therapy may improve clinical care and patient outcomes. Methods: As of 2/1/2019, we enrolled 50 patients on a multi-institutional, prospective study measuring circulating tumor DNA(ctDNA) minimal residual disease (MRD) in r/r DLBCL patients undergoing treatment with Axi-cel. Using an next generation sequencing-MRD assay (Adaptive Biotechnologies; Seattle WA), ctDNA levels were measured pre, 0, 7, 14, 21, 28, 56, 90, 180, 270, and 365 days following Axi-cel infusion. A pre-planned comparison between EDTA, Streck, and CFD tubes for the initial 10 enrolled patients determined the CFD tube provided optimal analyte stability over 144 hours following sample collection. CFD tubes are being used to collect all study samples. Results: 24 subjects have 3 or more months clinical follow up and their treatment ctDNA MRD significantly associated with clinical outcomes. A day 28 landmark analysis shows 12 patients were MRD negative and 12 patients were MRD positive as defined by detection of none or any tumor-associated ctDNA, respectively. 10 of 12 MRD+ patients subsequently developed progressive disease. In contrast, only 2 MRD- patients subsequently progressed and the 10 other patients remain in a CR. (p = 0.0033, Fisher's exact test). With a median follow up of 237 days, median PFS after Axi-cel infusion for day 28 MRD+ vs. MRD- patients is 93 days vs. not reach, p = 0.0010 by Log-rank test. Median OS for day 28 MRD+ vs. MRD- patients is 281 days after Axi-cel infusion vs. not reach, p = 0.0399 by Log-rank test. Conclusions: After Axi-cel infusion, day 28 ctDNA-based MRD significantly associates with PFS and OS and identified early at-risk patients prior to progression. These results provide a rationale for designing MRD-based risk-adaptive CAR T-cell clinical trials.

e15117 Background: Management of advanced-stage PCa frequently requires multimodal therapy and there is a hypothesized benefit of consulting with multiple specialists prior to commencing active tre...

e16550 Background: Substantial uncertainty exists about the benefits and harms of many oncology drugs in real-world settings, creating challenges for patients, providers, payers, and policymakers. ...

6000 Background: Although an FDA guidance is available to direct the development and inclusion of PROs in preapproval clinical research towards drug approval and labeling, no such guidance exists i...

e16617 Background: Each year, more than 18,000 randomized control trials are published and thousands of other clinical studies conducted. Despite this, systematic reviews intended to inform clinica...

3620 Background: Management of stage III colon cancer (SIIICC) frequently focuses on cancer-specific survival, yet overall survival and adverse events also impact the net clinical benefit of cancer...

4655 Background: Disparities in access to health care across demographic groups have been widely documented for primary therapies of PCa and among patients (pts) with early-stage PCa. Less is known...

3613 Background: Clinical trials have demonstrated a survival benefit of oxaliplatin (OX)- or irinotecan (IRI)-based combination chemotherapy regimens for treatment of stage IV colon cancer patient...

e14069 Background: Randomized controlled trials and real world comparative effectiveness studies have suggested survival benefits with adjuvant oxaliplatin (OX)-based regimen in stage III colon can...

1104 Background: The NCCN GLs are the standard of care for the treatment of women with metastatic breast cancer (mBC). The primary aim of the current project is to assess concordance between the NC...

1092 Background: The prognosis for women with metastatic breast cancer (MBC) is worse for those who have triple negative MBC (TNMBC). Few reports have examined TNMBC in an elderly population. The US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database provides information on estrogen receptor (ER) status and progesterone receptor (PR) status but does not record human epidermal growth factor receptor 2 (HER2) status, making identification and analysis of TNMBC patients challenging. Methods: Females over the age of 65 with stage IV breast cancer were identified in the SEER-Medicare database. Patients with a prior history of breast cancer were excluded. Those who were (1) ER negative, (2) PR negative, (3) had an administrative claim for HER2 test, and (4) did not receive trastuzumab were classified as potential TNMBC (p-TNMBC). Results: Of 1,755 MBC patients who met the inclusion/exclusion criteria, 313 (17.8%) were p-TNMBC. p-TNMBC were younger than other MBC (76.0 vs. 77.6 ...

1032 Background: The NCCN GLs provide the standard of care for the treatment of women with metastatic breast cancer (mBC). The primary aim of the current project is to assess concordance between the NCCN GL recommendation for drug therapy and care received using the PM database (DB). The PM is a patient (pt) care DB that incorporates medical and pharmaceutical claims data for younger managed-care patients. Methods: Claims for pts diagnosed with metastatic breast cancer from 2002 to 2008 were examined. Overall, 26,476 women with metastatic breast cancer were identified. Median age was 40 years. Results: 26,260 (99%) patients were identified as premenopausal with 7,005 (28%) receiving antiestrogen (AE) therapy. Until 2005, the NCCN GLs recommended luteinizing hormone-releasing hormone (LHRH) agonists as an optional compliment to AE therapy for mBC. Prior to 2005, 37 of 2,838 pts (1%) received LHRH agonists. After 2005, 3% received nonconcordant therapy with LHRH agonists. After 2005, the NCCN GLs recommend ...

3603 Background: Cancer patients are at increased risk of venous thromboembolism (VTE). VTE risk varies with cancer treatments and patient clinical and sociodemographic characteristics, including a...

4658 Background: To date, docetaxel (D) is the only chemotherapy agent that has provided a survival benefit to metastatic castration resistant PCa patients (pts). The objective of this study was to...

e16074 Background: The survival benefit of D in treatment of hormone refractory PC (HRPC) has been established in the TAX327 trial, but it is unclear how this benefit would translate in a heterogeneous population. This study sought to simulate the survival impact of D in a population of older pts with M1 PC on androgen deprivation therapy (ADT). Methods: A combination of TAX327 trial data and SEER-Medicare (SM) data were used. In pts age 69+ and randomized to D (every 3 weeks, D3P) or mitoxantrone (M), trial data showed a survival benefit for D. Accordingly, SM pts age 69+ diagnosed with M1 PC between 1994 and 2002 and receiving only ADT were selected. Graphical plots and statistical tests were used to find best-fitting parametric survival functions for D3P, M, and SM pts. The survival benefit for D was imposed on unadjusted and covariate-adjusted SM survival curves. The simulated benefit was assessed at 12 mos and 24 mos post-diagnosis of M1 PC in SM pts. Results: There were 326 TAX327 trial pts (D3P = 159, M = 167) used in the analysis. Median survival was 15.7 mos (12.6 - 19) in the M arm and 18.9 mos [17 - 21.8] in the D3P arm (p = 0.03). There were 3,515 SM pts, based on inclusion criteria. Median survival benefit of D was 3.2 mos based on Kaplan-Meier estimates and 2.4 mos using parametric curves in the TAX327 69+ group. Following covariate-adjustment in the SM sample, at 12 mos post-diagnosis, the median survival in mos was 61.7 (CI 36.3 - 87) in the ADT group and 62 (CI 37.6 - 87.1) in the simulated ADT+D group (i.e., 0.3 mos simulated benefit of D). A 0.8 mos simulated benefit was found if D was initiated 24 mos post diagnosis (in pts more likely to have HRPC). Conclusions: The survival benefit of docetaxel from the TAX327 trial is attenuated in a heterogeneous SEER-Medicare sample, and the simulated survival benefit is larger among patients who are more likely to have hormone refractory prostate cancer. [Table: see text]

e17509 Background: The association between physician referrals and treatment receipt has been established in other disease settings. The impact of time to a medical oncologist or hematologist/oncologist (MOH) visit on survival has not been examined in patients (pts) with advanced prostate cancer (A-PC). The objective of this study is to determine whether the time to a MOH visit is associated with survival. Methods: The SEER-Medicare database was used for the analysis. Pts aged >65 diagnosed with A-PC between 1994 and 2002 and who visited a urologist post-diagnosis were included. Pts who saw a MOH before the urologist visit were excluded. For pts who saw a MOH, time to a MOH visit was identified using the diagnosis date and the urologist visit as starting points. Survival models were used to examine the effect of the time (in months) to MOH visit on survival, controlling for demographic, clinical, continuity-of-care, and ecological measures. Results: There were 6,498 pts in the sample (mean age 76 years, 82% White race). PC-specific mortality was 38%. Two-thirds (67%) of patients did not visit a MOH after visiting a urologist. Among those with a visit to a MOH, an additional month from diagnosis till the MOH visit was positively associated with PC mortality (HR: 1.03; p < 0.001) - i.e. a shorter time to a MOH visit was associated with PC survival. Similar results were obtained using the month of the urologist visit as the starting point (HR: 1.02; p < 0.001). Conclusions: Among A-PC patients who are referred to an oncologist, each additional month between diagnosis/urologist visit and the oncologist visit is associated with an increased relative risk of mortality. [Table: see text]

1037 Background: Onset of anthracycline-induced cardiotoxicity is well documented. However, information regarding the time of onset varies depending on literature. The purpose of this study was to compare the risk of cardiotoxicity among three cohort groups: anthracycline-containing-chemotherapy (ACC), no-anthracycline-containing-chemotherapy (NACC), and no-chemotherapy (control) groups. Methods: A retrospective cohort study was designed using commercial managed care claims database. Adult subjects (≥18) diagnosed with breast cancer, between January 1, 2002 to December 31, 2005, (index-period) were followed for 24 months. Subjects with a previous cardiotoxic events (CE), breast cancer diagnosis, or anthracycline-use 12-months prior to index date were excluded. Index date was the first chemotherapy claim date for ACC and NACC and non-chemotherapy medication claim date for controls. Cohorts were matched by index date and year of birth. CE was defined based on ICD-9-CM and Healthcare Common Procedure Coding System codes. Risk of CE was evaluated using a logistic model with and without adjusting for confounders. Results: 21,106 subjects were classified as ACC (n = 3,428), NACC (n = 7,125), and controls (n = 10,553). NACC cohort was significantly (p < 0.01) older (mean age: 62 years ±12.5) compared to ACC (53±9.7) or control cohorts (59±12.5). ACC cohort had a higher (p < 0.01) average degree of comorbidity, (1.8±0.8) compared to NACC (1.6±0.9) or control (1.3±0.8) as measured by Charlson comorbidity-index. Higher rates of CE were found within the ACC group compared to NACC and controls as early as month 3 post index-date and remained consistent over 24 months. At month 12 post index-date, 14% (n = 485) of ACC and 5% (n = 381) of NACC had CE compared to 3% (n = 310) of controls. After adjusting for all baseline differences, the odds ratio of CE compared to controls was 3.98 (95% CI: 3.27–4.85), and 1.31 (95% CI: 1.11–1.54) for ACC and NACC cohorts, respectively. The total mean costs were $59,287, $20,528, and $11,600, among ACC, NACC, and control cohorts respectively. Conclusions: Compared to NACC and controls, ACC cohorts had significantly higher risk of cardiotoxic events and seen as early as month 3 post treatment initiation. [Table: see text]

e17513 Background: ADT remains standard treatment for pts with M1 PC, with radiation (RT) and chemotherapy (CT) providing additional palliation. This population-based analysis evaluated if long-term survivors (LT) receiving ADT possessed different characteristics relative to short-term survivors (ST). Methods: Pts age >/= 66y in SEER Medicare diagnosed with M1 PC between 1998 and 2002 and receiving ADT with or without subsequent CT were identified. Median overall survival (OS) for the sample was used as a cut-off to categorize ST and LT pts. Within these categories, demographic, and clinical characteristics were evaluated. Results: 2,665 ADT pts were first identified who had median OS of 26 months (95% CI 24.0 - 27.0). 1,349 pts died at [Table: see text]

e17548 Background: Docetaxel and paclitaxel are widely used in treating breast cancer (BC), and both have hematologic toxicity commonly managed by costly growth factors (GFs). However, the extent of GFs use in real-world clinical practice has not been well documented. Methods: The Georgia Oncology Specialist Database was used and contained chemotherapy, medical and pharmacy claims, and lab results for nearly 170,000 patients with various types of cancer (2003–2008). Patients with stage I-III BC receiving docetaxel- or paclitaxel-containing regimens as adjuvant therapy were followed from 1 week prior to docetaxel or paclitaxel (index drug) initiation to the earliest of death, loss to follow-up, switch in taxane, or end of 90-day period post last dose of index drug. Incidence of GFs use per person-year was compared using univariate negative binomial (NB) model, median time to first GFs use was compared using Wilcoxon test. Multivariate analyses were performed on number of utilizations and time to first utilization adjusting for potential confounders. Results: Compared with paclitaxel (n = 433), docetaxel cohort (n = 216) had lower incidence per person-year of erythroid stimulating agents (ESAs) use (8.01 vs. 11.72, p = 0.008), while similar incidence of myeloid growth factors (MGFs) use (8.51 vs. 5.07, p = 0.541). Lower MGFs utilization in docetaxel patients (ratio of number of utilization = 0.821, p = 0.033), and similar ESAs utilization (ratio of number of utilization = 0.920, p = 0.305) were found. While descriptive analysis showed paclitaxel patients received first ESAs sooner than docetaxel patients (median length: 23 vs. 7 days, p < 0.001), and no difference in time to first MGFs use (median 8 days for both); multivariate analyses found docetaxel patients received first MGFs sooner (ratio of days = 0.828, p = 0.039), and no difference in time to first ESAs use (ratio of days = 1.091, p = 0.419). Conclusions: This analysis suggests that docetaxel is associated with lower utilization of MGFs. Studies examining the economic impact of GFs use associated with taxanes will need to be conducted. A potential limitation of this study is that the potential selection bias may not be fully adjusted. [Table: see text]

e17001 Background: For the treatment of head and neck cancer (HNC), different modalities (chemotherapy, radiation, surgery, or chemoradiotherapy) can be used either independently or in combination with others. Information regarding real-world treatment pattern is limited. The purpose of this study was to identify common treatment pathways and associated costs. Methods: The study was performed using data from a large U.S. commercial managed care claims database. Adult subjects (≥18) diagnosed with HNC between January 1, 2006, to December 31, 2006, (index-period) were identified based on a pre-selected ICD-9-CM codes. All subjects were HNC diagnosis-naïve 12 months prior to their index dates (first date of HNC diagnosis) and followed for 12 months post index date. Treatment modalities were identified based on the Healthcare Common Procedure Coding System used in the U.S. Pathways were constructed by reflecting time of and between modality administration claims. Results: 6,570 subjects were identified. The average age was 61 years (±14.9) and 44% (n = 2869) were female. Midwest (31%) and east (31%) region had a higher (p < 0.01) representation, compared to south (20%) and west (18%). Only 2,257 subjects (34%) received some type of treatment modality and were categorized into 20 mutually exclusive treatment pathways. Of these, 82% (n = 1,843) received single modality, 18% (n = 398) received a combination of 2, and 0.7% (n = 16) received a combination of 3 modalities. Among single modality pathways, radiation (34%; n = 619) was most common, however, cheomoradiotherapy (26%; n = 485) had the highest average patient cost ($98,440). Within double modalities, radiation followed by chemotherapy (24%; n = 95) was most common, however, chemoradiotherapy followed by surgery (4%; n = 16) had the highest average cost ($146,374). Within triple modalities, surgery followed by radiation then chemotherapy (50%; n = 8) was most common and costly ($95,868). Conclusions: The most common treatment pathways one year post HNC diagnosis used a single modality; however, the average patient costs within multiple modalities were higher. Further study is required to investigate if these patterns are comparable to current guideline recommendation. [Table: see text]

5160 Background: Appropriate staging is critical for the successful management of prostate cancer patients. Differences in tumor extent and the likelihood of being appropriately staged exist across...

8090 Background: C improves quality of life and survival in adv (Stage 3B w/ effusion and stage 4) NSCLC in clinical trials. Little is known about actual patterns of C and survival effects among E....

6574 Background: Despite effectiveness of adj Ch for Stage 3 CC, prior research documented lower tx rates in E and African American (AA) pts. This population-based study identified sociodemographic...

7549 Background: Little is known about patterns of tx for elderly w/ LA NSCLC ( IIIa, IIIb w/o effusion). Combined modality tx (CMT) (chemotherapy, C and radiation, R) is indicated for “fit” patien...

4014 Background: Although sociodemographic disparities in colon cancer (CC) treatment (tx) have been documented, less attention has focused on age disparities. We estimated the modifying effect of ...

6607 Background: A randomized phase III trial of sunitinib vs. IFN-a as first-line therapy for patients with mRCC is ongoing. An interim analysis of this study demonstrated superiority for the primary endpoint, progression-free survival (PFS), in the sunitinib arm vs. the IFN-a arm (median PFS = 11 months [95% CI: 10–12] vs. 4 months [95% CI: 4–6]; P No significant financial relationships to disclose.