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IMPORTANCE: In clinical trials supporting the regulatory approval of oncology drugs, solid tumor response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Calculation of RECIST-based responses requires sequential, timed imaging data, which presents challenges to the method’s application in real-world evidence research. OBJECTIVE: To evaluate the feasibility and validity of a novel real-world RECIST method in assessing tumor burden associated with therapy for a large heterogeneous patient population undergoing treatment in routine clinical practice. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used physician-abstracted data pooled from retrospective, multisite electronic health record (EHR) review studies of patients treated with anticancer drugs at US oncology practices from 2014 through 2017. Included patients were receiving first-line treatment for thyroid cancer, breast cancer, or metastatic melanoma. Data were analyzed from March through August 2020. EXPOSURES: Undergoing treatment with immunotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES: Tumor response was classified according to RECIST guidelines (ie, change in sum diameter of target lesions) post hoc with measurements derived from imaging scans and reports. RESULTS: Among 1308 completed electronic case report forms, 956 forms (73.1%) had adequate data to classify real-world RECIST response. The greatest difference between physician-recorded responses and real-world RECIST–based responses was found in the proportion of complete responses: 118 responses (12.3%) vs 46 responses (4.8%) (P

71 Background: With the advent of newer non-cytotoxic therapies for aPC, early integration of hormonal therapies (HT), and expansion of services within urology practices [e.g., radiation therapy (RT) and immunotherapy], urology practices are playing a larger role in the management of patients with aPC. In this descriptive study, we sought to assess the differences between medical oncologists (oncs) and urologists (uros) as they pertain to referral patterns and treatment decisions of men with aPC. Methods: Virtual meetings held in August 2020 convened oncs and uros of diverse US regions and practice types with experience treating prostate cancer (PC) to better understand perceptions around the management of patients with PC. Participants submitted responses via web-based pre-meeting surveys and real-time polling. All responses are summarized using descriptive statistics. Results: 66 oncs and 69 uros participated. The advisors were mostly community-based and see on average 20+ patients per day. 75% of uros estimated they refer ≤25% of all of their patients with PC to oncs and 75% of oncs reported that > 50% of their patients with PC referrals are from uros. Other referring physicians identified include primary care (76%), radiation oncs (46%), or hospitalists (40%). Uros perceive oncs as co-managers (86%) for their patients with aPC and rarely (9%) transfer the care of their patients completely to oncs. Referrals from uros to oncs are driven by the need for chemotherapy (chemo) (52%) or progression to metastatic castration-resistant PC (mCRPC) (22%). Oncs reported that upon referral, these patients with PC have already been exposed to HT (75%), RT (66%), and/or surgery (43%). For second-line treatment of asymptomatic patients with mCRPC, oncs most commonly prescribe HT (60%) and chemo (23%), while uros most commonly prescribe sipuleucel-T (45%) and HT (38%). For second-line treatment of patients with mCRPC and symptomatic bony disease, oncs most commonly prescribe chemo (44%) and radium-223 (34%), while uros most commonly prescribe radium-223 (47%) and HT (22%). Conclusions: Uros refer patients with aPC to oncs for chemo. Uros prefer to treat with non-chemo options when possible and retain oncologic care for most of the patients’ cancer journey. The need for chemo is a major reason for referral from uros to oncs. The impact of these provider preferences upon patient outcomes in the real world needs further research. [Table: see text]

There are persistent knowledge gaps in the management of older patients with advanced lung cancer. Despite significant advances in the treatment over the past decade, mortality from lung cancer continues to increase in patients over age 70 years (1). Thus, advances in the treatment of lung cancer have minimally impacted this large subgroup of population. While patients 70 years or older account for almost half the patients with lung cancer, they are typically under-represented on clinical trials (1).

Introduction Non-Small Cell Lung Cancer (NSCLC) is an aggressive malignancy with poor overall survival that accounts for up to 85% of lung cancer diagnoses. The use of immunotherapy in the form of checkpoint inhibition, to enhance the immune system's ability to attack malignant cells, has been a promising addition to treatment options in advanced NSCLC. Results Such therapeutic agents aimed at the Programmed Death 1 (PD-1) receptor or Programmed Death Ligand 1 (PD-L1) have revealed promising results against many types of cancer including NSCLC. Examples of these agents include nivolumab, pembrolizumab, BMS-936559, atezolizumab, and MEDI4736, of which the first two are approved by US FDA in the second line treatment of advanced NSCLC. Discussion Impressive improvements in objective responses from PD-1 blockade were found in both first line therapy as well as treatment after progression on platinum based therapy. In addition, the safety profile is favorable with significantly lower grade 3-4 adverse events compared to standard of care. The optimal selection criteria and factors that show an increased response to therapy are still being determined.

BACKGROUND Frailty has been suggested as a construct for oncologists to consider in treating older cancer patients. Therefore, the authors assessed the potential of creating a deficit-accumulation frailty index (DAFI) from a largely self-administered comprehensive geriatric assessment (CGA). METHODS Five hundred patients aged ≥65 years underwent a CGA before receiving chemotherapy. A DAFI was constructed, resulting in a 51-item scale, and cutoff values were examined for patients in the robust/nonfrail (cutoff value, 0.0

Lung cancer disproportionately affects the elderly. Aging is typically associated with higher risk of comorbidity, declines in physical, organ, and cognitive function, and diminished social support. Hence the management of a disease as complex and potentially lethal as lung cancer in this population is challenging. Despite most patients with lung cancer being elderly, most high-level evidence has been derived from studies that included younger patients and only a minority of the fit elderly. This article reviews the literature on the care of older adults with lung cancer. The evolving role of geriatric assessment in lung cancer is discussed.

Introduction: Tisagenlecleucel (tisa-cel) is a chimeric antigen receptor (CAR) T-cell therapy approved by the United States (US) Food and Drug Administration (FDA) for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, and adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least 2 lines of systemic therapy. Real-world data on the safety of tisa-cel are limited, particularly in the pediatric and young adult patient ALL indication. Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and Cellular Therapy (CT) Registry presented at the American Society of Hematology Annual Meeting in 2019 found that efficacy and safety outcomes in 105 patients treated with tisa-cel for the ALL indication (Grupp 2019) and 47 treated for the LBCL indication (Jaglowski 2019) were largely similar to the clinical trials. Because tisa-cel is the only CAR T-cell therapy currently approved for 2 distinct indications in 2 distinct populations, we sought to further characterize the real-world adverse event (AE) profile of tisa-cel in each indication. In this large-scale analysis, we utilized the FDA Adverse Events Reporting System (FAERS) database to assess tisa-cel-related AEs in both the ALL and LBCL indications. Methods: The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. The database was queried for cases involving tisa-cel (and its trade name) in patients up to 25 years of age for the ALL indication, from the FDA approval date (August 30, 2017) through March 31, 2020; and in patients age ≥18 years for the LBCL indication, from the FDA approval date (May 1, 2018) through March 31, 2020. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Patient characteristics and AEs were summarized using descriptive statistics; comparisons of the proportion of AEs by indication were made using the Chi-square test with statistical significance determined at a two-sided α=0.05. Results: A total of 687 cases were retrieved (428 pediatric or young adult ALL, 259 adult LBCL); 94% of the cases were classified as serious. The median age among ALL cases was 13 years (range 0.5-25 years) and the median age among LBCL cases was 65 years (range 18-89 years) (Table). For both indications, cytokine release syndrome (CRS) was the most commonly reported reaction term (56.5% of ALL cases and 53.7% of LBCL cases). Some clinical features of CRS, including pyrexia, hypotension, and tachycardia, were reported more frequently among ALL cases compared with LBCL cases (pyrexia 51% vs. 41%; hypotension 25% vs. 16%; and tachycardia 9% vs. 5%, for ALL versus LBLC cases, respectively). A greater proportion of ALL cases reported immune effector cell-associated neurotoxicity syndrome (ICANS), including headache and seizure (11% and 3% respectively, vs. 3% and Conclusion: In this, the largest real-world analysis of AEs associated with tisa-cel to date, we found statistically significant differences in AE patterns between ALL and LBCL. A greater proportion of cases under the ALL indication reported ICANS, infections, and some CRS clinical features, including pyrexia, hypotension, and tachycardia. Out of specification test results showed trends similar to those reported from the CIBMTR CT Registry, where a higher proportion of LBCL patients had cell viability Disclosures Zettler: Cardinal Health: Current Employment. Feinberg:Cardinal Health: Current Employment. Balanean:Cardinal Health: Current Employment. Gajra:Cardinal Health: Current Employment.

Introduction: Poly (ADP-ribose) polymerase inhibitors (PARPi's) represent a newer class of antineoplastic agents targeting cancers with defective DNA-damage repair. PARPi's indications include subtypes of ovarian, fallopian tube and primary peritoneal cancer as well as subsets of patients with breast pancreatic and prostate cancers. There are currently 4 PARPi approved by the Food and Drug Administration (FDA): olaparib (approved 12/19/2014), rucaparib (approved 12/19/2016), niraparib (approved 3/27/2017), and talazoparib (approved 10/16/2018). The incidence of AML/MDS is known to be increased following chemotherapy, with a standardized incidence ratio (observed number of cases of AML/MDS among those treated with chemotherapy/expected number of cases in the general population) of 5.8 among patients with ovarian cancer, and 3.8 among patients with breast cancer (Morton et al, JAMA Onc 2018). All 4 PARPi also carry the potential risk of AML/MDS as an adverse event (AE), but a causal relationship has not been established. Notably, almost all patients treated with a PARPi would have exposure to cytotoxic chemotherapy prior to or during PARPi therapy. For patients treated with PARPi's in clinical trials, the duration of therapy prior to cases of AML/MDS emerging ranged from Methods: The FDA Adverse Events Reporting System (FAERS) database was queried for AEs associated with any of the 4 approved PARPi's, from the date of the initial FDA approval for each agent (irrespective of the indication) through March 31, 2020. The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. Cases reported outside the United States were excluded. The proportion of AML/MDS reports was analyzed overall and by PARPi. To account for the variation in length of time on the market due to the different approval dates, reports of AML/MDS for each PARPi were analyzed in the first 17 months after approval (the post-marketing period for the most recently approved agent). The indication for which the PARPi was used, the sex and age of the patient experiencing the AE, and the seriousness and outcome of the AE were assessed. Comparisons of the proportion of AML/MDS cases by agent were made using the Chi-square test; statistical significance was determined at a two-sided α=0.05. Results: A total of 12823 post-marketing AE reports were associated with PARPi's, with 88 (0.7%) reporting cases of AML/MDS (Table). The largest proportion of AML/MDS cases were associated with olaparib (54 of a total of 2121 AE reports; 2.5%, p Conclusions: Our retrospective analysis found that AML/MDS associated with PARPi's was reported rarely in the post-marketing setting, and that 60% involved olaparib. This study is limited by its retrospective design, and the possibility of under-reporting of cases to the FAERS database. Additionally, the time elapsed since approval differed by agent, and lower observed incidence of AML/MDS for some agents may reflect the limited duration of surveillance. No data is available in the case reports regarding length of exposure to chemotherapy. This real-world analysis complements existing clinical trial data and provides insight into AML/MDS associated with 4 different PARPi's in clinical practice. Disclosures Gajra: Cardinal Health: Current Employment. Zettler:Cardinal Health: Current Employment. Klink:Cardinal Health: Current Employment. Feinberg:Cardinal Health: Current Employment.

162 Background: There has been an increased emphasis on patient-reported outcomes (PROs) in recent oncology trials, and the benefits of incorporating PRO assessments during routine care have been established. The aim of the present study was to assess the perceptions, adoption and barriers to implementation of PROs in community practices during routine care. Methods: A live meeting in September 2019 surveyed US-based community oncology health care providers (HCPs), including medical oncologists/hematologists and advanced practice providers (APPs; defined as nurse practitioners and physician assistants) regarding their perceptions of PROs and their adoption of PROs during routine patient care. Participants completed both a web-based premeeting survey and live queries captured via audience response system. Data were summarized using descriptive statistics. Results: 71 HCPs (51 medical oncologists/hematologists and 20 APPs) participated. HCPs described their practices as: urban 50%, suburban 37%, and rural 13%. Over 80% reported having collected PRO data from their patients. Over 90% indicated that PROs are important to guide their treatment of patients, irrespective of the data sources (clinical studies or in real-world). Commonly collected PRO data included disease symptoms (66%), activities of daily living (62%), physical function (61%) and adverse events (59%). The NCCN Distress Thermometer (41%) was reported as the most common PRO instrument used during routine oncology care (Table). Despite understanding the importance of implementing PROs, 54% indicated that more resources (software and incentive systems) are needed, and 53% said that discussing PRO results with each patient is critical to facilitate the collection and utilization of PRO data. 84% were unaware of results of a seminal study which demonstrated that PROs improve quality of life and survival (Basch et al 2016, 2017). Conclusions: Most of the community oncology providers surveyed collected PRO data and acknowledged its value. However, more resources are needed to increase collection and use of PROs during routine care. Education directed towards community oncology providers is needed to highlight the value that PROs can add in cancer care. [Table: see text]

75 Background: In the value-based era, policymakers have begun incorporating quality of life (QoL) components into payment models, such as the Merit-based Incentive Payment System (MIPs), Oncology Care Model (OCM), and Accountable Care Organization (ACO), to increase accountability. This qualitative research study sought to understand how providers address their patients’ QoL issues in a value-based environment. Methods: A live meeting in September 2019 brought together community oncology healthcare providers (HCPs) from across the United States. Participants submitted their demographic information via a web-based pre-meeting survey and their responses pertaining to patient QoL via an audience response system during the live meeting. Participant responses and their practice demographics were analyzed using descriptive statistics. Results: 71 HCPs participated in this live market research program: 51 medical oncologists/hematologists (herein referred to as physicians) and 20 nurse practitioners or physician assistants (herein referred to as APPs). 50% of physicians and 25% of APPs were from privately owned community practices. Half of HCPs indicated that their practices are collecting and reporting QoL data through value-based programs: 28% of physicians and 60% of APPs were in OCM-participating practices. Regarding accountability, over 80% of HCPs strongly agreed that they have a role in improving patients’ QoL. However, 32% of physicians and 25% of APPs agreed that their payment should be tied to patients’ QoL improvement. According to HCPs, the top factor impacting patients’ QoL was symptom and symptom burden (83%). To address QoL in their patients, HCPs reported addressing patients’ psychosocial needs (78%), implementing survivorship care planning (76%), and using nurse navigators (69%). 70% of physicians and 95% of APPs were confident that their patients have reliable resources for managing their QoL issues. Conclusions: HCPs recognize their role in improving patients’ QoL, and their practices have made several transformations to improve patients’ QoL; they are confident that their patients have resources for managing QoL issues. However, many HCPs disagree with linking QoL improvements to their payment. Further studies are needed to understand QoL from patients’ perspectives in the value-based environment.

286 Background: Quality of life (QoL) is commonly assessed in oncology clinical trials. However, it is unclear if oncology healthcare providers (HCPs) perceive value in these metrics or if they impact clinical practice. We sought to assess the real-world utilization of QoL data and barriers to its adoption among US community oncology providers. Methods: Medical oncologists/hematologists, and advanced practice providers (APPs) participated in a survey to assess their perceptions and the utility of QoL data for routine practice during a live meeting in September 2019. Responses were captured via a web-based premeeting survey and an audience response system during the live meeting. Participant characteristics and responses were summarized using descriptive statistics. Results: A total of 71 HCPs (51 physicians and 20 APPs) participated. Regarding perceptions of QoL in oncology, 50% of physicians and 32% of APPs reported aligning with the sentence “It is important to have QoL, but efficacy is obviously the most critical endpoint.” HCPs reported that QoL may outweigh overall survival (OS) in certain clinical scenarios, such as in end-of-life (81%), frail patients (67%), or metastatic tumors (62%). When selecting between two agents with similar efficacy, safety was the most important factor (78%), followed by QoL (40%). 64% of physicians utilized aggregate QoL data from registrational trials or real-world studies to keep informed about QoL of different treatments, while 69% of APPs relied on their personal or practice experiences. 85% of physicians and 84% of APPs responded that it is important to perform formal QoL assessments during routine patient visits. 88% of HCPs expected that QoL/patient-reported outcomes (PRO) collection will increase their workload. Patient burden (58%) and provider resources (43%) were other barriers for QoL/PRO collection. HCPs were largely split regarding their understanding of QoL versus PRO, with 34% reporting that PRO was a subset of QoL and 28% reporting that QoL was a subset of PRO. Conclusions: Efficacy and safety are prioritized as clinical endpoints among oncology HCPs; however, there are certain clinical scenarios where QoL may provide more impactful data for HCPs in managing patients. Barriers remain to successful collection of QoL, and there is a need for further education among HCPs regarding PROs and QoL.

129 Background: Older adults are disproportionately affected by cancer and may be under-treated due to concerns for adverse events or may suffer excessive toxicity from standard cancer treatments due to comorbidity and diminished physiologic reserve. A geriatric assessment (GA) can assist with risk stratification, inform treatment decisions and improve outcomes in older adults with cancer. This descriptive study aimed to assess knowledge, perceptions, and utilization of GA instruments among community oncologists/hematologists (cOH) with an overall goal to identify actionable disparities in the management of older adults with cancer. Methods: Questions about GA in the care of older adults with cancer were developed by two medical oncologists (AG and BAF) and presented to cOH with diverse geographic representation at live meetings and a preceding web-based survey between September 2019 and February 2020. Descriptive statistics were used to analyze the results. Results: Of the 349 participants, the response rate was 100%. The cut-off age used to define older adults by cOH was: ≥ 65 years (22%), ≥ 70 years (39%), and ≥75 (32%). The proportion of patients aged ≥ 70 years in their practices was reported as: 26-50% (48%) and > 50% (22%). Most cOH (60%) performed no formal GA to inform treatment decisions. The two most common reasons for not performing GA were: “Too cumbersome to incorporate into routine practice” (44%), and “Adds no value beyond the comprehensive history and physical exam” (36%). cOH awareness of validated GA/related instruments was: Mini-Mental State Exam (MMSE; 63%), Comprehensive GA (CGA; 37%) and CARG (Cancer and Aging Research Group) GA tool (22%); 22% were not aware of any validated instruments. Outside of clinical trials, the most frequently used validated GA instruments were: MMSE (54%), CGA (23%), CARG (12%), and CRASH (9%). For older adults with cancer, ECOG performance status and comorbidities were the two GA-related surrogate factors utilized in treatment decisions (88% and 73%, respectively). Conclusions: A majority of US community oncologists do not incorporate formal GA with validated instruments in the decision-making for older patients with cancer due to lack of time, resources and awareness. Education directed towards community oncologists may change perception and practice.

206 Background: GA is a multidisciplinary assessment consisting of the following domains: physical function, comorbidity, cognition, mood, social support, nutrition and medication review. Conducting a GA with validated instruments to assess these domains has been shown to improve outcomes in older adults with cancer [Soo, et al ASCO 2020]. The utilization of validated GA tools and its domains versus use of other surrogates from history and physical exam (HPE) for risk-stratification in older adults in the community practice setting is unclear. In this survey-based study, we assessed the knowledge of GA and the methods used to evaluate GA domains among cOH. Methods: Questions pertaining to GA and the care of older adults with cancer were developed by two medical oncologists (AG and BAF) and presented to cOH with diverse US geographic representation at live meetings and via web-based questionnaire between September 2019 and March 2020. Results were analyzed using descriptive statistics. Results: Of the 173 participants surveyed, 59% reported performing no GA, while 13% and 28% reported performing GA on all and selected older adults, respectively. When presented with a list of daily living activities, over half of cOH were unable to correctly identify all activities of daily living (ADLs) and instrumental ADLs (56% and 70%, respectively). The top 2 methods used by cOH to assess physical functional were the ECOG performance status (82%) and HPE (42%). For assessment of cognition, most cOH used HPE (78%) or the Mini Mental State Exam (MMSE; 12%). Social support was assessed via HPE (44%) or GA (27%). cOH reported that medication review is performed by an office staff (medical assistant 31%, nurse 12%, pharmacist 5%), with the physician signing off on the information reported in the chart irrespective of who entered the medication information (50%). Regarding chemotherapy dosing in older adults with cancer, only 7% utilized GA to inform chemotherapy dose; 48% reported starting at a lower chemotherapy dose with intent to escalate, while 33% reported starting at the standard dose with intent to de-escalate if toxicity is encountered. Lastly, 27% stated that oncologists are not adequately equipped to care for older adults with cancer given the complexity involved. Conclusions: Many cOH do not utilize validated instruments to assess the domains of GA. There also appear to be knowledge gaps regarding individual domains of GA. There is a need to further the education of cOH regarding the components and value of GA in older adults with cancer.

e21717 Background: Pem+carbo+pac or nab-pac are approved first-line (1L) treatments for metastatic squamous NSCLC since 10/30/2018. Difference in real-world outcomes of these triplet combinations are unknown. Methods: Providers from community oncology practices in the USA reviewed the charts of consecutive NSCLC patients initiating 1L treatment with either pem+carbo+pac (“pac”) or pem+carbor+nab-pac (“nab-pac”) from 06/01/18-12/31/18; data were collected 11/22/2019-12/23/2019. Patient characteristics, treatment patterns, grade 3/4 toxicities, disease response, date of progression/death were retrospectively abstracted into an electronic case report form (eCRF). Univariate statistics were used to compare demographics, clinical characteristics and treatment patterns between cohorts. Overall survival (OS) from 1L was calculated using the Kaplan-Meier method. A Cox proportional hazards model was used to compare the risk of death between the two cohorts adjusted for multiple variables. Results: eCRFs were completed for 254 patients: nab-pac = 115, pac = 139. Median follow-up was 13.1 mos in both cohorts. No differences in demographics/clinical characteristics were noted (table). Median duration of therapy was 3.9 mos (nab-pac) and 3.8 mos (pac) (p = 0.58). Objective response rate: nab-pac = 69.6%, pac = 69.8% (p = 0.96). Receipt of maintenance therapy: nab-pac = 44.4%, pac = 48.9% (p = 0.47) . Median time to progression was 6.4 mos for nab-pac (n = 32) and 3.5 mos for pac (n = 29) (p = 0.10). 13.9% of nab-pac and 7.9% of pac patients had grade 3/4 toxicities (p = 0.16). At data cut-off, 18 nab-pac (15.7%) and 30 pac (21.6%) patients were deceased. Median OS from initiation of 1L was not reached. 12-month OS: nab-pac = 87.8% (95% CI: 81.8-93.8), pac = 79.3% (95% CI: 72.5-86.2). Adjusting for sex, age, race, PD-1 expression level, charlson comorbidity index (CCI) and ECOG-PS patients treated with nab-pac had a 40% reduction in mortality risk (HR = 0.55, 95% CI: 0.30-1.01, p = 0.05). Conclusions: No significant differences in demographics and clinical characteristics between patients treated with nab-pac or pac were observed. Median duration of treatment was equivalent with a marginally longer 12-month survival rate, and a lower adjusted mortality risk, among patients treated with nab-pac. [Table: see text]

e13095 Background: TNBC accounts for 10-20% of all breast cancer and has poor prognosis. Guidelines now list atezolizumab with nab-paclitaxel (ANP) as preferred for mTNBC w/ PD-L1 expression > 1%. We sought to assess current mTNBC prescribing and sequencing preferences for first-line (1L), second-line (2L), and third-line (3L) therapy among U.S. community oncologists (c-oncs). Methods: C-oncs were presented 4 hypothetical mTNBC clinical scenarios (CS 1-4) via web-based survey. CS differed by PD-L1 expression, menopausal status, prior adjuvant therapy and nature of metastases (bulky liver, lung, bone) but were otherwise uniform in terms of being asymptomatic, BRCA negative, with identical response extent and duration of each line of therapy. Respondents selected their preferred treatment for 1L, 2L, and 3L in each CS in the following categories: single agent (SA) chemotherapy, combination chemotherapy (CC), or ANP. The proportion of c-oncs selecting each treatment approach per CS for each line of therapy was calculated. We describe these preference patterns and how these may deviate from current guidelines. Results: 47 c-oncs participated from across the U.S. (northeast = 23%, midwest = 28%, south = 32%, west = 17%): mean years in practice was 22.7 and mean number of mTNBC patients under treatment was 18.8. The proportion of c-oncs preferring SA, CC or ANP per CS per line of therapy is listed in the table. Deviations from guidelines include preferences for: 1L ANP despite PD-L1 < 1% (26% in CS 1 and 4); 1L CC (45%) in asymptomatic bone only disease (CS1); 2L CC (19-34%) in asymptomatic visceral metastases (CS 2, 3 and 4). The SA 2L (74%)/3L (90%) preferences: capecitabine (36% 2L; 18% 3L) and eribulin (24% 2L; 35% 3L). Gemcitabine + carboplatin was the preferred CC regimen in 2L (50%) and 3L (28%). Conclusions: There is deviation from current guidelines in the treatment preferences for mTNBC patients among c-oncs, specifically the preference for ANP in PD-L1 negative patients and CC in 2L and 3L for asymptomatic patients. [Table: see text]

7070 Background: NSCLC is the most common non-AIDS-defining cancer in PLWHA with an estimated prevalence 2-5 times that of PWoHA. Guidelines now support treatment of NSCLC among PLWHA to follow those for PWoHA. However, PLWHA have been often excluded from cancer clinical trials that test novel agents including immunotherapy (IO). This study aimed to assess differences in systemic therapy patterns for advanced NSCLC among PLWHA and PWoHA in the RW. Methods: Adult patients with ≥2 claims for NSCLC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics and comparisons by HIV status made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 60,278 NSCLC PWoHA who received systemic therapy. Of 1,344 PLWHA with NSCLC, 239 (18%) received systemic therapy. PLWHA differed significantly from PWoHA: median age at diagnosis (58 v 68 years), male preponderance (66% v 47%), payer mix (Medicare 26% v 42%; Medicaid 21% v 7%), Charlson Comorbidity Score (median 6 v 1), depression (13% v 5%) and liver disease (8% v 2%), respectively (all P< 0.01). Differences in common systemic therapies among PLWHA v PWoHA include use of first line (1L) carboplatin + paclitaxel (28% v 19%; P< 0.01), 1L erlotinib (6% v 11%, P= 0.02) and 2L gemcitabine (10% v 4%, P< 0.01). IOs were used in 1L among 43 (18%) and 7,149 (12%) of PLWHA v PWoHA, respectively ( P< 0.01). RW surrogates for PFS: median duration of 1L therapy was shorter among PLWHA (1.8 v 2.3 months, P< 0.01); median times from 1L initiation to 2L were similar (5.4 v 4.9 months; P= 0.48). Similar proportion of patients continued onto 2L (32% and 30%) and 3L (10% and 9%) among PLWHA and PWoHA, respectively (all P> 0.05). Total time from diagnosis to last follow-up (RW surrogate for overall survival) was 12.8 v 15.5 months in PLWHA and PWoHA ( P= 0 .07). Conclusions: PLWHA are younger at diagnosis of NSCLC and have higher comorbidity. Important differences in regimen selection and IO utilization exist across PLWHA and PWoHA. PLWHA have shorter 1L than PWoHA. Given higher risk and younger age at diagnosis, additional research is needed to establish screening and treatment guidelines for NSCLC in PLWHA.

2058 Background: Adequate gender representation in clinical trials of new drugs is critical in order to accurately detect possible differences in response and toxicity (Özdemir et al, JCO 2018). The under-representation of women in oncology clinical trials has been previously described, however data on registrational trials, which are the basis for drug approval and inform the prescribing information, is lacking. We conducted an analysis of the trials supporting Food and Drug Administration approval of oncology drugs over a 5-year period to evaluate the representation of women vs. men. Methods: Prescribing information for novel new drugs approved from 2014-2018 was reviewed for the proportions of men and women in the evaluable population of the supporting clinical trials. Sex-specific cancers were excluded. Prevalence estimates for the indications were obtained from the Surveillance, Epidemiology and End Results database and the published literature. A participation to prevalence ratio (PPR) was calculated for each trial by dividing the percentage of women in the trial by the percentage of women in the disease population. A PPR value closer to unity represents even gender distribution and the range 0.8-1.2 is considered to reflect an acceptable representation of women. Data are presented using descriptive statistics. Results: A total of 46 oncology drugs were approved based on 56 trials enrolling 13,862 patients (7941 [57%] men; 5,921 [43%] women). Of the 56 trials, 38 (68%) had a PPR within the 0.8-1.2 range, 15 (27%) fell between 0.4-0.7, and 3 (5%) had a PPR of 1.3. The proportion of trials with unbalanced gender representation was comparable for hematological malignancy and solid tumor indications and did not improve over time. Fewer unbalanced trials were Phase III or employed a randomized design. Nine of the 18 (50%) unbalanced trials enrolled

e19010 Background: Antiretroviral therapy (ART) has brought life expectancy among PLWHA on par with PWoHA, but the disparity in cancer incidence and mortality among PLWHA remains high. Hepatocellular carcinoma (HCC) is 4 times more common in PLWHA and an important cause of mortality. Guidelines now support treatment and management of cancer among PLWHA to follow those for PWoHA, but PLWHA have been excluded from registrational trials of novel agents. This study aimed to assess real-word differences in demographics and systemic therapy patterns for HCC among PLWHA and PWoHA. Methods: Adult patients with ≥2 claims for HCC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics, and comparisons across HIV status were made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 9,904 HCC PWoHA who received systemic therapy. Of 862 PLWHA with HCC, 162 (19%) received systemic therapy. PLWHA differed significantly from PwoHA: median age at diagnosis (60 v 63 years), male preponderance (84% v 71%), geography (Northeast, 41% v 19%; West, 22% v 45%), Charlson Comorbidity Score (median 7 v 1), depression (11% v 6%), chronic pulmonary disease (20% v 12%), liver disease (66% v 52%) and kidney disease (17% v 7%, all P< 0.05), respectively. First line (1L) therapy differed among PLWHA and PWoHA: sorafenib (34% v 25%), everolimus (1% v 4%), and doxorubicin-based regimens (42% v 33%; all P< 0.05). IOs were used in 1L and 2L among 584 (6%) and 223 (15%) of PWoHA and among 8 (5%) and 6 (19%) PLWHA, respectively (all P> 0.05). Median times from 1L start to 2L were numerically shorter among PLWHA and PWoHA (4.7 v 5.5 months; P= 0.77). The minority of patients among PLWHA and PWoHA continued onto 2L (20% and 15%, P> 0.05) and 3L (7% and 3%, P< 0.01), respectively. Conclusions: HCC is diagnosed at younger age among PLWHA v PWoHA. Important differences in comorbid disease burden in addition to HIV can impact clinical decision making in PLWHA. Future real-world research is needed to understand disparities in outcomes of PLWHA and develop guidelines specific to this group.

12015 Background: Timely integration of palliative care in the management of patients with advanced cancer is a quality benchmark in oncology. However, PC is often underutilized as evidenced by delays in identification of appropriate patients, in referrals to a PC service, and in enrollment to hospice. Jvion has developed a prescriptive analytics solution, the Machine, which combines AI algorithms with machine learning techniques and applies them to clinical and exogenous datasets to identify patients with a propensity for poor outcomes. The Machine was applied to risk for patients’ mortality within next 30 days, and recommended patient-specific, dynamic, and actionable insights. Use of the Machine requires no additional documentation within the electronic health record (EHR) and the insights generated can be integrated back in to any EHR to help inform the care plan. Herein, we report the results of a study evaluating the impact of AI-driven insights on PC utilization at a large community oncology practice. Methods: All patients were scored weekly using the Machine PC vector. The Machine risk stratified the patients and generated recommendations for the provider to consider as they developed a care plan. Patients identified as “at risk” by the Machine were assessed for a supportive care visit (PC referral) and then were referred as deemed clinically appropriate. The average monthly rates of PC consults and hospice referrals were calculated 5 months prior to and for 17 months after the launch of the Machine in the practice. Results: The oncology practice has 21 providers managing an average of 4329 unique patients per month (PPM). The mean rate of PC consults increased from 17.3 to 29.1 per 1000 PPM pre and post Machine deployment respectively (+168%). The mean monthly rate of hospice referrals increased by 8-fold from 0.2 to 1.6 per 1000 PPM pre and post deployment respectively. Eliminating the first 6 months of Machine deployment to account for user learning curve, the mean rates of monthly PC consults nearly doubled over baseline to 33.0, and hospice referrals rose 12-fold to 2.4 per 1000 patients in months 7-17 post Machine deployment. Conclusions: This oncology practice found deployment of this novel AI solution to be feasible and effective at generating actionable insights. These AI driven insights could be incorporated into workflow and improved the decision-making for whether and when a patient should be referred to PC and/or hospice services for end of life care. Further study is needed to confirm the value of AI for management of cancer patients at end of life.

e14059 Background: Depression is common in patients with cancer and is associated with worse cancer treatment outcomes. Depression is often underdiagnosed/treated as cancer clinicians are focused on the complex aspects of therapy and care coordination. AI has a potential application in the identification of patients at high risk for depression. Jvion has developed a prescriptive analytics solution (the Machine), which uses AI algorithms and machine learning techniques applied to combined clinical and exogenous datasets to identify patients with a propensity for poor clinical outcomes. The Machine was applied to depression risk (within next 6 months), and recommended patient-specific, dynamic, and actionable insights. While the Machine requires no additional documentation within the electronic health record (EHR) to generate its insights, those insights can be integrated back in to any EHR. Herein, we report the results of a pilot study evaluating the impact of AI-driven insights on depression screening and management at a single oncology practice. Methods: All patients were scored weekly using the Machine depression vector. The Machine risk-stratified the patients and generated recommendations for the provider to consider as they developed a care plan. Patients identified as “at risk” by the Machine were assessed for depression (PHQ-9) by the clinical team regardless of prior screening results. The rate per 1000 unique patients per month (PPM) of depression screenings, case management evaluations, and antidepressant prescriptions were calculated for the 5 months prior to and 17 months post deployment of the Machine in the practice. Results: The oncology practice has 21 providers managing an average of 4329 unique PPM. The mean rate of depression screenings increased from 6.0 per 1000 PPM pre- deployment to 16.2 per 1000 PPM post deployment (+271%). The downstream workflow outcomes of case management evaluations increased from 11.6 to 21.4 per 1000 PPM (+184%) and antidepressant prescriptions increased from 9.2 to 15.5 per 1000 PPM (+168%) pre and post-implementation respectively. The providers reported high satisfaction with the use of the AI solution in depression screening. Conclusions: This oncology practice found deployment of the Jvion AI solution to be feasible. The Machine-generated insights for depression risk were actionable, could be incorporated into workflow, and increased the number of patients identified. If confirmed in larger studies, AI-driven insights may improve the identification and management of depression in patients with cancer.

Introduction The phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified nab-paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. Methods Chemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of nab-paclitaxel 100 mg/m2 days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received nab-paclitaxel monotherapy (100 mg/m2 days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs). Results 11/40 treated patients (27.5%; 95% CI, 14.60–43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued nab-paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99–7.00) and 7.7 (95% CI, 4.93–13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%). Conclusion This nab-paclitaxel–based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data.

Introduction Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age. Methods Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801). Comparisons among patients who were 65 years and older and 70 years and older were performed for TTF (primary endpoint), reasons for early chemotherapy cessation, grade 3+ adverse events, and overall survival. Results Among 1006 patients, 460 (46%) were older than 65 years of age. One hundred forty-five older patients (32% of this age cohort) completed all six planned chemotherapy cycles as did 170 (32%) younger patients. Median TTF was 2.9 months (95% confidence interval: 2.7– 3.2) in older patients and 3 months (95% confidence interval: 2.9–3.5) in younger patients; adjustment for performance status and stratification by chemotherapy by trial yielded no statistically significant age-based difference in TTF. However, reasons for early chemotherapy cessation differed between age groups (multivariate p = 0.004). Older patients were less likely to discontinue from cancer progression (41% versus 55%) and more likely from toxicity or patient choice (16% and 15%, respectively) compared to younger patients (13% and 6%, respectively). Older patients were more likely to experience grade 3+ adverse events (86% versus 79%) with no statistically significant difference in survival. An age cutpoint of 70+ years showed no difference in TTF, a lower trend of early cessation due to cancer progression, and somewhat shorter older patient survival. Conclusions TTF was comparable between older and younger patients; but different, age-based, and potentially modifiable reasons account for it.

BACKGROUND: Falls in older adults with cancer are common, yet factors associated with fall-risk are not well-defined and may differ from the general geriatric population. This study aims to develop and validate a model of factors associated with prior falls among older adults with cancer. METHODS: In this cross-sectional secondary analysis, two cohorts of patients aged ≥65 with cancer were examined to develop and validate a model of factors associated with falls in the prior 6 months. Potential independent variables, including demographic and laboratory data and a geriatric assessment (encompassing comorbidities, functional status, physical performance, medications and psychosocial status), were identified. A multivariate model was developed in the derivation cohort using an exhaustive modeling approach. The model selected for validation offered a low Akaike Information Criteria value and included dichotomized variables for ease of clinical use. This model was then applied in the validation cohort. RESULTS: The development cohort (N=498) had a mean age of 73 (range 65-91). Nearly one-fifth (18.2%) reported a fall in the prior 6 months. The selected model comprised 9 variables involving functional status, objective physical performance, depression, medications and renal function. The AUC of the model was 0.72 (95% confidence intervals 0.65-0.78). In the validation cohort (N=250), the prevalence of prior falls was 23.6%. The AUC of the model in the validation cohort was 0.62 (95% confidence intervals 0.51-0.71). CONCLUSION: In this study, we developed and validated a model of factors associated with prior falls in older adults with cancer. Future study is needed to examine the utility of such a model in prospectively predicting incident falls.

The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation.

Background Studies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy-related adverse events in older, early-stage breast cancer patients. Methods This study is a pre-planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years. Results The median age of this 331-patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five patients (46%) described a social network of 0–10 people; 110 (35%) of 11–25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support. Conclusion Although social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study. Copyright © 2015 John Wiley & Sons, Ltd.

Background: In CALGB-49907 (NEJM 2009;360:2055), older patients (pts) with ESBC were randomized to standard adjuvant chemo (AC or CMF versus capecitabine). The objective of this secondary QoL analysis is to assess if pts’ BL chemo preference (CP, defined as high or low), is associated with the following during and after completion of chemo: self and professional-reported toxicity, changes in mental health, function, QoL, recurrence-free (RFS) and overall (OS) survival. Patients and Methods: Of 633 trial pts 350 participated in the QoL substudy; 145/350 pts completed the BL assessment regarding CP. CP was measured by asking the amount of benefit women would require to choose adjuvant chemo in a hypothetical situation, irrespective of chemo agents. Women who chose chemo for an increase in OS of ≤12 months (mo) were designated as high chemo preference (HCP) and those who chose >12 mo were designated low chemo preference (LCP). CP associations were evaluated with: BL perception of self-health and perceived QoL on chemo; patient reported outcomes (PROs), changes in function and QoL (based on EORTC-QLQ-C30); anxiety and depression (Hospital Anxiety and Depression Scale); observed grade 3-5 adverse events (AEs) by NCI common toxicity criteria (CTC v2.0). Pts were assessed at midtreatment and at 1, 12, 18 and 24 mo post-treatment. Chi-square tests, t-tests, and Cox models were used for categorical, continuous, and time-to-event variables, respectively. Results: The demographic and tumor characteristics of women (median age 71) who provided CP at BL were not different from women in the QoL subset or from non-QoL pts. 68/145 (47%) women had a HCP. CP groups did not differ based on age, surgery type, tumor and nodal stage, hormone receptor status, performance status, chemo assignment, education, marital or employment status except the LCP group had a higher proportion of white women (95% vs. 78%, p=0.004). At BL, there were no differences in perception of self-health based on CP but women with LCP predicted QoL on chemo to be worse than women with HCP (p=0.006) and reported greater nausea/vomiting. Mid-treatment, LCP pts reported worse nausea/vomiting, financial worries, and cancer symptoms. Post-treatment, LCP pts had worse constipation (at 1 mo) and financial worries (at 24 mo). There were no differences based on CP for dyspnea, pain, fatigue, insomnia, anxiety or depression at any timepoint. Mid-treatment, LCP women reported lower QoL and worse social, emotional and physical function compared to HCP women. These scores were not significantly different after treatment completion. LCP women had significantly higher rates of grade 3-5 AEs (53 vs. 34%, p=0.02) during treatment but these did not persist post-therapy. CP was not significantly associated with OS (HR =0.75, p=0.36) or RFS (HR=0.94, p=0.84). Conclusions: LCP at BL was associated with lower QoL, worse physical symptoms, AEs and function mid-therapy, but not mental health. Mid-therapy declines in women with LCP largely reversed post-therapy. This information may be useful for oncology professionals to counsel older ESBC pts with LCP receiving adjuvant chemo. Citation Format: Ajeet Gajra, Linda McCall, Hyman B Muss, Harvey J Cohen, Aminah Jatoi, Karla V Ballman, Ann H Partridge, Linda Sutton, Barbara A Parker, Gustav Magrinat, Jaqueline M Lafky, Arti Hurria. Association of patient preference for adjuvant chemotherapy (chemo) at baseline (BL) with toxicity, mental health, function, quality of life (QoL) and survival in older women with early stage breast cancer (ESBC) [CALGB 49907 Alliance] [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-07.

BACKGROUND Adjuvant chemotherapy after surgical resection improves outcomes for patients with early-stage non–small cell lung cancer (NSCLC). To the authors' knowledge, there are no published prospective trials to date of adjuvant chemotherapy after surgical resection administered exclusively in older patients. In the current study, the authors sought to evaluate the efficacy of adjuvant chemotherapy in older patients in a Veterans Health Administration cohort. METHODS Patients who underwent surgical resection for American Joint Committee on Cancer stages IB to III NSCLC between 2001 and 2011 were analyzed. Data regarding patient demographics and comorbidities, tumor characteristics, and primary treatment were collected. Patients were divided into 2 groups based on age at diagnosis: those aged

Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision.We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated.Among 500 patients (mean age 73, range 65-91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3-5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses.PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS.

SUMMARY Elderly patients constitute a substantial proportion of patients with advanced NSCLC. Several unresolved issues surround the treatment of elderly patients with NSCLC, including under-representation in clinical trials, the definitions of fit and unfit patients and the appropriate age cut-off for this population. Taken together, these factors have a large impact on the treatment of elderly patients with advanced NSCLC. An urgent need exists to develop new strategies for clinical trial design that may lead to improved outcomes in these patients. This review will address the existing barriers and controversies in the management of advanced NSCLC in the elderly, focusing on cytotoxic chemotherapy regimens. Results of clinical trials conducted in the elderly and those from planned subset analyses for age-unspecified trials will be provided, with a focus on recently reported studies. Outcomes from population databases reporting on this population in a nonclinical trial setting will be reviewed.

Purpose: Older adults compose the majority of patients with cancer in the United States; however, it is unclear how well geriatrics or geriatric oncology training is being incorporated into hematology-oncology (hem-onc) fellowships. Methods: A convenience sample of hem-onc fellows completed a (written or electronic) survey assessing their education, clinical experiences, and perceived proficiency in geriatric oncology during training; knowledge base in geriatric oncology; confidence in managing older adults with cancer; and general attitudes toward geriatric oncology principles. Results: Forty-five percent of respondents (N = 138) were female, 67% were based in the United States, and most (60%) were past their first year of training. Most fellows rated geriatric oncology as important or very important (84%); however, only 25% reported having access to a geriatric oncology clinic and more than one half (53%) reported no lectures in geriatric oncology. Fellows reported fewer educational experiences in geriatric oncology than in nongeriatric oncology. For example, among procedure-based activities, 12% learned how to perform a geriatric assessment but 78% learned how to perform a bone marrow biopsy ( P < .05). Of those completing the knowledge-based items, 41% were able to identify correctly the predictors of chemotherapy toxicity in older adults with cancer. Conclusion: Despite the prevalence of cancer in older adults, hem-onc fellows report limited education in or exposure to geriatric oncology. The high value fellows place on geriatric oncology suggests that they would be receptive to additional training in this area.

Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC-particularly those undergoing concurrent chemoradiation therapy-and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population.

Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non–small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC. Patients with COX-2 expression ≥ 2, performance status of 0 to 2, and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin plus pemetrexed for nonsquamous NSCLC and carboplatin plus gemcitabine for squamous histology. Patients were randomly assigned to celecoxib (400 mg twice per day; arm A) or placebo (arm B). The primary objective was to demonstrate improvement in progression-free survival in patients with COX-2 index ≥ 4 with hazard ratio of 0.645 with approximately 85% power at two-sided significance level of .05. Results The study was halted for futility after 312 of the planned 322 patients with COX-2 index ≥ 2 were randomly assigned. There were no significant differences between the groups (hazard ratio, 1.046 for COX-2 ≥ 4). Subset analyses evaluating histology, chemotherapy regimen, and incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Elevation of baseline urinary metabolite of prostaglandin E2, indicating activation of the COX-2 pathway, was a negative prognostic factor. Values above the third quartile may have been a predictive factor. Conclusion COX-2 expression by IHC failed to select patients who could benefit from selective COX-2 inhibition. Urinary metabolite of prostaglandin E2 may be able to identify patients who could benefit from COX-2 inhibition.

A nocebo is an inert substance associated with adverse events. Although previous studies have examined the positive (placebo) effects of such inert substances, few have examined negative (nocebo) adverse event profiles, particularly in older patients who have higher morbidity and can experience frequent and severe adverse events from cancer therapy.This study focused on placebo/nocebo-exposed patients who participated in 2 double-blind, placebo-controlled, cancer therapeutic studies, namely, North Central Cancer Therapy Group trial NCCTG 97-24-51 and American College of Surgeons Oncology Group trial Z9001, with the goal of reporting the comparative, age-based adverse event rates, as reported during the conduct of these trials.Among the 446 patients who received only placebo/nocebo and who were the focus of the current report, 161 were aged ≥65 years at the time of respective trial entry, and 5234 adverse events occurred. Unadjusted adverse event rates did not differ significantly between patients aged ≥65 years and younger patients (rate ratio, 1.01; 99% confidence interval, 0.47-2.02), and the findings were similar findings for grade 2 or worse adverse events and for all symptom-driven adverse events (for example, pain, loss of appetite, anxiety). Adjustment for sex, ethnicity, baseline performance score, and individual trial resulted in no significant age-based differences in adverse event rates. Similar findings were observed with an age threshold of 70 years.Adverse events are equally common in older and younger cancer patients who are exposed to nocebo and thus require the same degree of clinical consideration regardless of age. Cancer 2017;123:4193-4198. © 2017 American Cancer Society.

Adenocarcinoma is the most common type of non-small-cell lung cancer (NSCLC). Adenocarcinoma with epidermal growth factor receptor (EGFR) mutations accounts for 8%-30% of all cases of NSCLC depending on the geography and ethnicity. EGFR-mutated NSCLC usually responds to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). However, there is eventual loss of efficacy to TKIs due to development of resistance. The most frequent cause for resistance is a second EGFR mutation in exon 20 (T790M), which is encountered in up to 62% of patients. Osimertinib is one of the third-generation EGFR TKIs with a high selective potency against T790M mutants. In Phase I trial of osimertinib in advanced lung cancer after progression on EGFR TKIs, the response rate and disease control rate were 61% and 95%, respectively. A subsequent Phase II (AURA2) trial demonstrated a disease control rate of 92%, a response rate of 71%, a median duration of response of 7.8 months, and a median progression-free survival of 8.6 months. Osimertinib was approved by the US Food & Drug Administration in November 2015 for patients whose tumors exhibited T790M mutation and for those with progressive disease on other EGFR TKIs. In this review, we address the role of EGFR TKIs in the management of EGFR mutation lung cancer and the mechanisms of resistance to TKIs with a focus on the role of osimertinib. Data from completed trials of osimertinib, ongoing trials, as well as novel diagnostic methods to detect EGFR T790M mutation are reviewed.

By the year 2030 older adults will account for 20% of the U.S. population1, almost doubled from 20052. Cancer is a disease of aging; over half of all cancer diagnoses and almost three quarters of cancer deaths occur in patients older than 653. The development and progression of comorbid conditions and the accelerating loss of spouses, friends and loved ones may make older adults with cancer more vulnerable to anxiety and depression4. The rate of anxiety in older oncology patients has been cited to be as high as 23%5, while depression in older oncology patients ranges from 17–26%6. Despite the various challenges faced by geriatric oncology patients, recent studies have suggested that age may actually serve as a protective factor against cancer-related psychological distress7. Distress is an umbrella term encompassing factors such as quality of life, anxiety, and depression. When teasing apart distress, age may not buffer against all facets of distress. For example, in a study of older men (age 50 and older) with prostate cancer, while increased age was associated with reduced anxiety (p < 0.01), increased age was also associated with greater depressive symptoms (p < .01)8. The percentage of men scoring above the cut-off for depression consistently increased with age. Despite the burgeoning geriatric oncology population and the importance of understanding how age may be related to constructs such as anxiety and depression, there has been limited further exploration of changes in anxiety and depression related to age within an older population of patients. Depression and anxiety are associated with poorer treatment outcomes9, reduced ability to make treatment decisions, decreased adherence to lengthy treatment and longer hospital stays10–14, and suicide1,15. Given the serious consequences of unrecognized and untreated depression and anxiety, it is important for clinicians to know if older adults are more vulnerable, and which variables might serve as signals to screen for depression and anxiety among this population. The current study seeks to explore the relationship between age, anxiety and depression within an older oncology population. Based on the literature, we hypothesized that anxiety would decrease with age while depression would increase with age.

BACKGROUND Despite clinical trials demonstrating improved survival with adjuvant chemotherapy (AC) for patients with American Joint Committee on Cancer stages I to III non-small cell lung cancer (NSCLC), it is unclear whether this survival benefit extends to broader populations. The current study evaluated patterns of AC use and examined the impact of AC on survival. METHODS A retrospective analysis was conducted of patients in the Veterans Affairs Central Cancer Registry diagnosed with stages IB to IIIA NSCLC between 2001 and 2008. Descriptive statistics were used to examine patterns of AC use over an 8-year time period. Cox proportional hazards regression analyses were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CIs) to compare mortality risk among patients treated with and without AC. RESULTS Among 14,306 patients with stages IB to IIIA NSCLC, 4929 underwent surgery and 22% of these received AC. The percentages of patients diagnosed in 2001 through 2003, 2004 through 2005, and 2006 through 2008 receiving AC were 7.0%, 29.8%, and 29.5%, respectively. There was no survival benefit with AC noted for patients diagnosed between 2001 and 2003, but AC was associated with improved survival for the period between 2004 and 2005 (HR, 0.78; 95% CI, 0.67-0.91) and 2006 through 2008 (HR, 0.79; 95% CI, 0.69-0.91). Of those patients receiving AC, 89% received platinum-doublet chemotherapy. Carboplatin remained the most common agent, although cisplatin use reached 43% in the period between 2006 and 2008. The HR for cisplatin relative to carboplatin was 0.96 (95% CI, 0.80-1.15). CONCLUSIONS There was a significant increase in the use of AC between 2001 and 2008 and AC was associated with an improvement in overall survival. Cancer 2014;120:1939–1947. © 2014 American Cancer Society.

Introduction The ASH Annual Meeting is a venue for presentation of outcomes data from key clinical trials in hematologic malignancies and novel drug classes used to treat them. The approval of two CAR-T therapies, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel), in the treatment of large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), has ushered in a new class of drugs, i.e. cellular therapy. At ASH 2018, Nastoupil et al. presented data from a retrospective analysis of the characteristics and outcomes of patients with relapsed/refractory LBCL, including DLBCL, treated with commercially available axi-cel CAR-T therapy at academic centers in the United States (Nastoupil LJ, et al. Blood. 2018;132[Suppl 1]:91). The authors found that early outcomes of real-world patients receiving axi-cel therapy were comparable to those observed in the clinical trial population, despite >40% of these patients failing to meet the clinical trial eligibility criteria. At a live meeting in February 2019, we sought the perceptions of community hematologists and oncologists (H/O) regarding their use of, referrals for and barriers to CAR-T therapy as well their perception of the value of the real-world evidence (RWE) presented. Methods A live meeting in February 2019 convened H/O with geographic representation from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. Participants submitted their demographic responses via a web-based survey prior to the meeting and data impression responses via an audience response system at the live meeting. Results Among the 59 H/O who participated in this live market research program on February 22-23, 2019, 61% identified their primary specialty as hematology/oncology and 34% medical oncology. Only 27% of H/O had attended the 60th ASH Annual Meeting in December 2018. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. One-third have been in practice for over 20 years, one-third for 11-20 years and one-third for 10 or fewer years. This group sees an average of 20+ patients per day and reported B-cell non-Hodgkin lymphoma as one of the three most common hematologic malignancy they managed. 28% of H/O indicated that they have referred one patient and 24% have referred 2-5 patients for CAR-T therapy since the first approval on August 30, 2017. Of those H/O who had referred patients for CAR-T therapy, 45% indicated that none of their patients had yet received the infusion. The top two barriers to prescribing/recommending CAR-T therapy, as reported by the H/O, were the cumbersome logistics of administering therapy and following patients (52%), and the cost of the therapy (46%). Other concerns included high toxicity (24%) and lack of long-term survival data (19%), but not lack of knowledge of CAR-T therapy (2%). Furthermore, 87% of H/O agreed with the assertion that due to the limitations of randomized clinical trials, RWE is necessary to inform clinical practice. After review of the information presented on the real-world use of axi-cel, 73% of H/O indicated that this information is likely to cause them to recommend CAR-T therapy for more of their patients with DLBCL. Conclusions There is significant interest in adopting and using CAR-T therapies in LBCL amongst community H/O. This group does not perceive itself as lacking in knowledge regarding CAR-T therapy. The significant barriers of logistics and cost are potential deterrents to appropriate use. These results can inform stakeholders (manufacturers, payers, hospitals and practices) regarding the need to improve processes and develop payment models to address cost in order to facilitate access of these agents to the appropriate patients. RWE is viewed favorably by the vast majority of community H/O to inform clinical practice, due to the limitations of randomized clinical trials. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction In the past 5 years, four drugs have received approval for the treatment of Chronic lymphocytic leukemia (CLL), with most of the data supporting their approvals presented at an ASH meeting. How treating hematologists and oncologists (H/O) incorporate these agents into their practice has implications for all stakeholders. We conducted market research with H/O to understand how CLL data presented at ASH 2018 might alter their treatment preferences. Methods A live meeting in February 2019 convened H/O. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions on the data and its potential impact on current practice. The presentations used included the following: 1) Alliance A041202: a phase III, randomized study in older patients with untreated CLL comparing ibrutinib ± rituximab with bendamustine + rituximab (BR) (Woyach JA, et al. Blood. 2018;132[Suppl 1]:6); and 2) E1912: a phase III, randomized study in younger patients with untreated CLL comparing ibrutinib + rituximab with fludarabine + cyclophosphamide + rituximab (FCR) (Shanafelt TD, et al. Blood. 2018;132[Suppl 1]:LBA-4). Participants submitted their demographic responses via a web-based survey and data impression responses via an audience response system at the live meeting. Results 59 H/O participated in this live market research on February 22-23, 2019 and identified their primary specialty as 61% hematologist/oncologist and 34% medical oncologist. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. Over one-third have been in practice >20 years and see an average of 20+ patients per day. In the prior 3 months, 31%, 27%, and 18% of the participants initiated first-line treatment on 1, 2, or 3 CLL patients, respectively. The most commonly preferred first-line treatments for CLL patients ≥65 years without del(17p) were: BR (38%), ibrutinib (34%), anti-CD20 monotherapy (17%), and FCR (7%). Based on the results of the Alliance A041202 trial, 88% are likely to use single-agent ibrutinib as their preferred first-line therapy for older CLL patients, 45% very likely and 43% moderately likely. The most commonly preferred first-line treatments for CLL patients Conclusion Studies of newer mechanism of action drugs like Bruton's tyrosine kinase (BTK) inhibitors are perceived as compelling by treating oncologists and appear likely to replace more traditional chemotherapy-based regimens. The clinical, financial, and patient-centric outcomes of such rapid changes to standard of practice warrant further research. Disclosures Feinberg: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Gajra:Cardinal Health: Employment.

Introduction: Registry data indicate that 20% or more of Hodgkin lymphoma (HL) patients are ≥60; these HL patients have been labeled as elderly as their treatment has been associated with more toxicity, a higher relapse rate, and greater mortality relative to younger patients. The characteristics of HL in elderly patients differ from those in younger patients and may represent a biologically more aggressive disease. Further, elderly patients generally have a greater comorbidity burden than their younger counterparts, which may contribute to their under-representation in clinical trials. Nivolumab (NIVO) and pembrolizumab (PEMBRO) are both approved for treating relapsed/refractory HL based on studies that largely enrolled younger patients, as only about 10% of enrolled patients in the pivotal trials that led to their United States (US) Food and Drug Administration (FDA) approval were ≥60 years of age. Whether adverse events (AEs) related to these immunotherapies differ between younger and older HL patients is unknown and may have important clinical and practice implications. Therefore, we reviewed all post-marketing case reports from the FDA Adverse Events Reporting System (FAERS) Database involving NIVO or PEMBRO for HL and compared AEs and outcomes by age. Methods: The FAERS database is a repository of anonymized reports for product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving NIVO or PEMBRO (and their respective trade names) from the FDA approval date for the HL indication (May 17, 2016 for NIVO; March 14, 2017 for PEMBRO) through March 31, 2019. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 126 cases were retrieved (117 involving NIVO, 9 involving PEMBRO). One hundred and fourteen of the 126 cases (90%) were categorized as serious. Median age of all patients involved was 56 (range 10-89); 53 of the cases (42%) involved patients age 60 or older (Table). Overall, 8 cases had an outcome categorized as life-threatening; 20 cases resulted in death; 2 resulted in disability; and 74 resulted in hospitalization. A higher proportion of cases involving younger patients were categorized under the reaction group "neoplasms benign, malignant and unspecified" (16% vs. 2%; p0.05). Conclusions: Although elderly patients comprise 20% of the HL patient population in the US, our post-marketing analysis indicates that AEs in this subgroup account for more than 40% of the total. This suggests that elderly HL patients experience a disproportional number of AEs compared to younger HL patients. While the types of AEs reported in post-marketing cases generally paralleled those observed in clinical trials of HL patients receiving NIVO or PEMBRO, hospitalizations and infections were more common in the elderly group. These differences in the adverse reactions and safety outcomes associated with PD-1 blockade therapy in HL patients may help inform clinical care and monitoring for AEs. Despite the inherent limitations of this study, our findings complement clinical trial safety data and provide insight into real-world trends in reported safety signals that merit further study. Disclosures Zettler: Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Gajra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Despite high cure rates (>75%) achieved in adults with classical Hodgkin Lymphoma (cHL) with modern chemotherapy, radiation, anti-CD30 therapy, and stem cell transplant (SCT), a minority of patients are refractory to primary chemotherapy or at relapse accounting for about 1000 deaths annually in the US. cHL has a bimodal distribution seen in young adults and a secondary peak in patients over age 60. While patients over age 60 comprise less than 25% of new cases, they account for over 60% of deaths from cHL signifying poor prognosis in this group. The approval of immune checkpoint inhibitors (IO) in cHL has offered patients another class of agents to achieve disease response. The two approved agents in this drug class, nivolumab (NIVO) and pembrolizumab (PEMBRO) were approved in R/R cHL in May 2016 and March 2017 respectively. The common adverse effects of immunotherapy (IO) in clinical trials include fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash, hypothyroidism and hypertransaminasemia. The objective of this real-world analysis is to assess the utilization of IO (NIVO and PEMBRO) in patients with cHL who have been treated outside of clinical trials and ascertain adverse events (AEs) and time to treatment discontinuation in patients aged ≥60 compared to those Methods: Patients with at least 1 claim for cHL and treated with either NIVO or PEMBRO in second line or later (2L+; i.e., R/R disease) from May 2016 to October 2018 were identified from the Symphony Integrated Dataverse, a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 73% of specialty prescriptions, 58% of medical claims, and 30% of hospital claims volume in the US. Patients included in the study cohort had a 6-month pre-index period with no claims with a diagnosis of HL, were at least 18 years old at initiation of NIVO or PEMBRO, and no evidence of participation in a clinical trial, including receiving NIVO or PEMBRO prior to their approvals (May 2016 and March 2017, respectively). Patient characteristics and treatment patterns were summarized using descriptive statistics. Median and 95% confidence interval (CI) for duration of IO agent were calculated using Kaplan-Meier estimates. Results: Of the 338 patients with R/R cHL treated with an immune checkpoint inhibitor, 247 (73%) received NIVO, and 91 (27%) received PEMBRO. Median age at initiation of the first IO agent in the R/R setting was 58 years (range 18-80), 48% were over the age of 60 and 59% were male. Nearly two-thirds (62%) had commercial insurance, and patients resided across all 4 US regions. Half (50%) of patients received their IO agent in second line (i.e., first therapy in RR setting), 31% in third line, and 19% in fourth line or later. With a median follow-up of 13.4 months from R/R disease, median time to discontinuation of IO agent was 5.7 months (95% CI 4.8-7.5). Most common AEs among at least 10% of patients during treatment with an IO agent were fatigue (22%), anemia (16%), dyspnea (14%), and cough (12%); anemia was more common among patients ≥60 years old (22%) compared to those Conclusions: IO therapy with both NIVO and PEMBRO is widely used in R/R cHL irrespective of age. Despite a lower incidence of cHL in patients ≥60 almost half (48%) of patients in this database treated with IO were older. Possible explanations include greater propensity of refractory disease in older adults and possible preference for IO agents given that the AE profile is distinct from that of cytotoxic chemotherapy. Almost half of IO is being used early in the course of disease in the 2nd line. The AE profile is similar to that reported in clinical trials and does not differ significantly by age with the exception of anemia, which was more common in patients aged ≥60 years. Time to treatment discontinuation did not differ by age or by the agent used. Despite its inherent limitations, this analysis adds real-world evidence to the safety and efficacy data of IOs in cHL outside clinical trials. Disclosures Gajra: Cardinal Health: Employment. Klink:Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction There has been a remarkable growth of new therapies for multiple myeloma (MM) in the last 5 years with 5 new agents approved by the FDA. Daratumumab is a human anti-CD38 monoclonal antibody previously approved as a single agent in relapsed/refractory (RR) MM and as combination in relapsed MM. Selinexor represents a novel first-in-class selective inhibitor of nuclear export (SINE) XPO1 antagonist in RRMM. The perception of practicing community hematologists and oncologists (H/O) regarding new information presented at major scientific meetings has implications for all stakeholders including patients, practices, payers, manufacturers and distributors. We conducted market research with H/O to understand how MM data presented at ASH 2018 and ASCO 2019 might alter their treatment preferences. Methods Live meetings in February and June 2019 convened H/O with geographic representations from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting or 2019 ASCO Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. The presentations used included the following: 1) MAIA: a phase III, randomized study in patients with transplant-ineligible newly diagnosed MM (NDMM) comparing daratumumab plus lenalidomide and dexamethasone (D-Rd) to lenalidomide and dexamethasone (Rd) alone (Facon T, et al. Blood. 2018;132[Suppl 1]:LBA-2); 2) CASSIOPEIA: a phase III, randomized study in patients with transplant-eligible NDMM comparing daratumumab plus bortezomib, thalidomide and dexamethasone (D-VTd) to bortezomib, thalidomide and dexamethasone (VTd) alone (Moreau P, et al. J Clin Oncol. 2019;37[15_suppl]:8003); and 3) STORM: a pivotal, phase II, single-arm study of selinexor and dexamethasone in patients with penta-refractory MM (Chari A, et al. Blood. 2018;132[Suppl 1]:598). Participants submitted their demographic responses via a web-based survey prior to the meetings and data impression responses via an audience response system at the live meetings. Results Among the 112 H/O who participated in these live market research programs on February 22-23 and June 21-22, 2019, 58% identified their primary specialty as hematology/oncology and 38% medical oncology. Only 27% of the 59 H/O at the February live meeting had attended the ASH 2018 in December 2018 and 43% of the 53 at the June live meeting had attended the ASCO 2019 in June 2019. The participants were mostly community-based physicians, 47% in private community and 48% in community practices owned by a hospital or academic center. 31% have been in practice for over 20 years, 39% for 11-20 years and 29% for 10 or fewer years. The majority of this group sees at least 16 patients per day and reported active MM as one of the three most common hematologic malignancies they manage. At the February 2019 live meeting, 79% of H/O in attendance indicated that, based on the results of the MAIA study, D-Rd is likely to become their standard of care for patients with NDMM who are ineligible for transplant. At the June 2019 live meeting, the majority of H/O in attendance indicated that bortezomib + lenalidomide + dexamethasone (VRd) was the regimen typically used for their transplant-eligible NDMM patients. After reviewing the data from the CASSIOPEIA study of D-VTd, 50% of H/O indicated that the results are practice-changing and will be widely adopted, but thalidomide will be substituted with lenalidomide (D-VRd). 65% of H/O who attended the February 2019 live meeting indicated that, if selinexor is approved by the FDA, they are very likely to consider it for their patients with RRMM. 76% of advisors indicated that selinexor's novel mechanism of action (MOA) is very clinically meaningful in MM. Qualitative data collected also denotes interest in seeing selinexor tested and moved to earlier lines of therapy akin to the development course followed by daratumumab. Conclusions The movement of daratumumab to the first-line setting was well received by the community H/O and their willingness to substitute IMiD drugs in the backbone regimen for transplant-eligible patients was notable. It is noteworthy that the interest in selinexor was high even prior to its FDA approval and especially driven by its novel MOA. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Acute Myeloid Leukemia (AML) is a biologically heterogeneous disease with poor outcomes despite aggressive induction chemotherapy (IC). Cytogenetics and mutational profile are used to inform subgroups of patients who are at high risk of relapse. Mutations in the fms-related tyrosine kinase 3 gene (FLT3) are detected in 30% of adults with newly diagnosed AML. The predominant (75%) FLT3 mutation, is an internal tandem duplication mutation (FLT3-ITD), which confers poor prognosis due to a high relapse rate. The addition of the multitargeted kinase inhibitor midostaurin to standard IC significantly prolonged overall survival (hazard ratio for death 0.77, p=0.016) among patients with AML and a FLT3 mutation. Midostaurin was approved by the United States Food and Drug Administration (FDA) in April 2017 for the treatment of adult patients with newly diagnosed FLT3+ AML, as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin IC and cytarabine consolidation. The recommended dose of midostaurin in AML is 50 mg twice daily with food on days 8 to 21 of each cycle of induction and consolidation chemotherapy followed by 50 mg with food as a single agent for up to 12 months. The objective of this study was to evaluate the utilization of midostaurin in AML in the real-world setting in the first year after its US approval and marketing. Methods: Patients with at least 1 claim for midostaurin (index date) between April 1, 2017 and October 31, 2018 and who had at least 1 claim with a diagnosis of AML in the 6-month pre-index period were identified from Symphony Health's Integrated Dataverse (IDV), a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 73% of specialty prescriptions, 58% of medical claims, and 30% of hospital claims volume in the US. Patients included in the study cohort had a 6-month pre-index period with no claims with a diagnosis of AML, were at least 18 years old at initiation of midostaurin, and no evidence of participation in a clinical trial. Patient characteristics and treatment patterns were summarized using descriptive statistics. Median and 95% confidence interval (CI) for duration of midostaurin were calculated using Kaplan-Meier estimates. Results: There were 708 patients with AML treated with midostaurin who met all study selection criteria. Median age at midostaurin initiation was 60 years (range 20-80), and 49% of patients were male. The majority (61%) had commercial insurance, and patients resided in all 4 US regions (43% West, 22% South, 18% Northeast, 16% Midwest). Midostaurin was given as first line therapy in 583 (82%) patients, as second line in 95 (13%) patients, and as third line or later in 30 (4%) patients (see Table). Among the 95 patients who received midostaurin as second line therapy, hydroxyurea monotherapy (n=24, 25%) and sorafenib monotherapy (n=23, 24%) were most common first line therapies. With a median follow-up of 5.9 months from initiation of midostaurin, the median duration of midostaurin treatment was 2.3 months (95% CI 1.9-2.6). Over half (51%) had an average daily dose of 100mg on their first fill, 25% had 50mg, 9% had 67mg, 5% had 25mg, and 10% had other doses. Conclusions: In this retrospective claims-based study, there is evidence of early uptake of midostaurin use in AML. However, majority of patients receive midostaurin as a single agent contrary to the approved schedule of initiating midostaurin concurrently with IC and with consolidation cytarabine. The median duration of midostaurin treatment was short at 2.3 months given that the recommendation is to continue it for 12 months after IC. Almost half the patients are started at a dose that is lower than the recommended dose, which may impact efficacy. Potential limitations of this dataset include a relatively short period of follow-up, retrospective design and low uptake post-marketing as some patients may have completed IC or missing data from midostaurin administered in the hospital. Barriers to the appropriate use of midostaurin in AML, if any, will need further exploration. Universal and timely testing for the FLT3 mutation is the essential first step to allow for including midostaurin as a part of IC for the appropriate utilization of this agent in FLT3 + AML. Disclosures Gajra: Cardinal Health: Employment. Klink:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Chopra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Systemic Mastocytosis (SM) is a rare neoplasm of myeloid origin characterized by an accumulation of abnormal mast cells in the bone marrow, liver, spleen, and skin and has a molecular signature of the KITD816V mutation, detectable in >90% of patients. Clinical findings include cytopenias, liver-function abnormalities, hypoalbuminemia, weight loss, ascites, and osteolytic bone lesions due to infiltration of various organs by the malignant mast cells. The indolent and smoldering subtypes of SM can have a long natural history but aggressive systemic mastocytosis (aSM), SM with associated hematological neoplasm (SMHN), and mast cell leukemia (MCL) subtypes are associated with poor prognosis at a median survival of 3.5 years, 2 years and 6 months respectively. In April 2017, the FDA approved midostaurin, a multitargeted kinase inhibitor for the treatment of adults with aSM, SMHN and MCL at a dose of 100mg twice daily based on achievement of response rate endpoint noted in an open label trial of midostaurin (Gotlib et al, NEJM 2016). Pre-midostaurin, the treatment options for aSM, SMHN and MCL were imatinib, cladribine, interferon or allogeneic stem cell transplant (ASCT). The objective of this retrospective study was to assess the uptake and utilization of midostaurin in patients with aSM, SMHN and MCL. Methods: Patients with at least 1 claim for midostaurin (index date) between April 1, 2017 and October 31, 2018 and who had at least 1 claim with a diagnosis of SM (ICD 10 code C96.2x or C94.3x) in the 6-month pre-index period were identified from Symphony Health's Integrated Dataverse (IDV), a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 73% of specialty prescriptions, 58% of medical claims, and 30% of hospital claims volume in the US. Patients included in the study cohort had a 6-month pre-index period with no claims with a diagnosis of SM, were at least 18 years old at initiation of midostaurin, and no evidence of participation in a clinical trial. Patient characteristics and treatment patterns were summarized using descriptive statistics. Median and 95% confidence interval (CI) for duration of midostaurin were calculated using Kaplan-Meier estimates. Results: Of the 38 patients with SM treated with midostaurin, 33 had a diagnosis of aSM and 5 had a diagnosis of MCL. The majority were female (61%) with a median age of 63 years (range 27-79) at diagnosis; 42% of these patients were 65 years or older (Table). The majority (66%) of patients had commercial insurance, and patients resided in all 4 US regions (34% South, 34% West, 18% Midwest, 11% Northeast). Nearly two-thirds (63%) of midostaurin use was in the first line setting, 32% was given in second line, and 5% was given in third line. Among the 14 patients with therapy prior to midostaurin, cladribine was most common (n=4, 29%), followed by hydroxyurea, interferon alfa-2b, brentuximab vedotin, and others (each n=2, 14%). Over two-thirds (68%) had an average daily dose of 200mg on the first fill, 5% treated at 100mg daily, and 26% with average daily doses Conclusions: In this retrospective claims based study, there is evidence of early uptake of midostaurin use in SM. Midostaurin was used in the first line setting in the majority of patients. The median duration of midostaurin treatment was short at 2.4 months especially when compared to a median treatment duration of 11.5 months in the pivotal trial. It is noteworthy that almost a third of patients were started on a lower than recommended dose which may compromise efficacy. The relatively short follow up may be another reason for the observed duration of response. Potential barriers to the appropriate use of midostaurin in SM such as lack of awareness, access, cost or delay in diagnosis due to its rarity will need further exploration. While the current claims-based dataset does not provide us the information, early, accurate diagnosis of SM is essential to timely utilization of midostaurin in the real-world setting. Further research and education may be needed to optimize the use of novel therapeutics in such orphan diseases. Disclosures Gajra: Cardinal Health: Employment. Klink:Cardinal Health: Employment. Chopra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Neurotoxicity is a major adverse event (AE) of CAR-T therapy with diverse presentation. When severe, it can be fatal, and may lead to neurologic sequelae as well as contribute to increased health care utilization, driving up cost of therapy. In clinical trials, the most common neurologic AEs with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia and anxiety. Fatal and serious cases of cerebral edema, leukoencephalopathy and/ or seizures have been reported with both agents. In this real-world analysis, we reviewed post-marketing case reports from the FDA Adverse Events Reporting System (FAERS). Database involving axi-cel or tis-cel for large B cell lymphoma (LBCL), with the dual objectives of characterizing the various components of neurotoxicity and assessing the association of neurological (neuro) AEs with demographic and treatment factors as well as with other AEs reported with CAR-T cell therapy use. Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The FAERS database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if patient age was unknown or if the case was reported outside the US. Of all patients reported to have neuro AEs, the frequency of various components was collected. The association of neuro AEs with patient age, concomitant AEs and key lab abnormalities were evaluated by Fisher's exact test, using a two-sided α=0.05 to determine statistical significance. Median age in each subgroup was compared using the Mann-Whitney U test. Results: In the 397 case reports identified, the majority of reactions (376, 95%) were classified as serious. Overall, 258 (65%) were reported to have neuro AEs, with "neurotoxicity" reported in 170 cases (66%); encephalopathy including CAR-T cell-related, metabolic and toxic in 92 cases (36%); seizures including status epilepticus, myoclonus and partial seizures in 12 cases (5%); stroke including cerebrovascular accident, hemiparesis, basal ganglia, brain stem, cerebellar and cerebral infarcts, motor dysfunction, facial and cranial nerve paralysis in 13 cases (5%); speech disorders including terms of aphasia, dysarthria, speech and language impairment in 55 cases (21%); amnesia and memory impairment in 18 cases (7%); brain or spinal cord edema and increased intracranial pressure in 6 cases (2%). Peripheral neuropathy was reported in 5 cases (2%). Symptoms of headache, tremors, dizziness and somnolence were reported in 30 (12%), 41 (16%) 3 (1%) and 34 (13%) cases respectively. Confusional state, delirium or agitation were reported in 61 cases (24%). Neuro AEs were associated with use of axi-cel vs. tis-cel (69% vs. 24%, p 0.05). Conclusions: Neuro AEs were common with CAR-T cell therapy in the real world and largely resembled those reported in clinical trials. Neuro AEs were associated with the agent used, age ≥65 as well as the presence of CRS, cardiac and psychiatric AEs but not with any of the laboratory values studied. The limitations of this study include its retrospective nature, potential under-reporting to FAERS and the relatively small number of patients in the tis-cel group due to its later approval and shorter time available for uptake compared to axi-cel. Despite these limitations, our findings can serve to inform clinicians' decision making when treating adult patients with CAR-T cell therapy. Further research is needed to better discern the etiopathology and biomarkers of neuro AEs in CAR-T cell therapy. Disclosures Gajra: Cardinal Health: Employment. Zettler:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) are chimeric antigen receptor (CAR) T-cell therapies that target CD19-expressing B cells. Both therapies have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least 2 lines of systemic therapy. The median age at diagnosis of diffuse LBCL is 66 years, with over half the cases occurring in patients over age 65. Patients >65 years have worse survival than younger patients. Despite this predilection for older age, only one quarter of the patients in the pivotal trials supporting approval of the 2 therapies were age 65 or older. An analysis of the safety of axi-cel in the pivotal ZUMA-1 trial showed no significant differences between the age Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if the age of the patient was unknown. Cases reported outside the US were excluded. Patient characteristics and adverse events were summarized using descriptive statistics. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 397 cases were retrieved (360 involving axi-cel, 37 involving tis-cel). The median age of the patients involved was 62 years (range 18-81), with 153 (39%) of the patients age 65 or older. The vast majority of reactions (376, 95%) reported to FAERS were classified as serious. Overall, 141 (36%) cases resulted in hospitalization; 33 (8%) cases had an outcome categorized as life-threatening; 46 (12%) cases resulted in death; 6 (2%) resulted in disability. The most common reaction in each age group was cytokine release syndrome (CRS), reported in 64% and 56% of patients Conclusions: This large-scale post-marketing report of CAR T-cell therapy associated AEs in the real world suggests differences based on age: patients ≥65 had a higher incidence of neurotoxicity and atrial fibrillation while younger patients had increased incidence of some CRS components, especially pyrexia and tachycardia. There was no demonstrable difference in deaths between the 2 groups, but younger patients had higher rates of hospitalization. This report provides real-world evidence for use of CAR T-cell therapy in patients ≥65 and can inform clinical care based on patterns of AEs observed. Potential under-reporting of cases to the FAERS database, the retrospective design of this study and limited data available in the case reports preclude interpretation of causality. Despite these limitations, our findings identified real-world trends in reported signals that complement clinical trial safety data and support further pharmacoepidemiologic study. Disclosures Zettler: Cardinal Health: Employment. Feinberg:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Gajra:Cardinal Health: Employment.