Leblanc, Thomas

Abstract Background: Anthracycline and cyclophosphamide (AC) is a highly emetogenic chemotherapy (HEC) regimen. Combination netupitant/palonosetron (NEPA) + dexamethasone (DEX) is guideline-recommended for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in HEC and moderately emetogenic chemotherapy. CMS’ OP-35 measure deems 30-day post-chemotherapy acute care as avoidable if involving nausea and emesis (NV) or any of 8 other toxicities. Results will be publicly reported and impact Medicare reimbursement. CMS (2017) found that 10% of >58,000 patients with avoidable acute care after chemotherapy involved NV. Because NEPA is new, insufficient real world data exist to assess its CINV resource use. CINV-related acute-care after NEPA prophylaxis in AC has been reported in a prospective clinical trial. Our aim was to compare these rates to those seen after prophylaxis with other antiemetics for AC outside of a clinical trial. Methods: Pre-specified endpoints in a prospective trial of oral or IV NEPA + DEX in AC included acute-care use (emergency [ED] visits or inpatient admissions [IP]) involving CINV, defined as emesis or rescue drug use ≤5 days after AC, and concomitant ED/IP in the same period. We also evaluated CINV-related acute care after non-NEPA prophylaxis for AC in breast cancer from 10/2012-8/2018 in IBM Explorys electronic health records. We age-matched patients 3:1 to the NEPA trial. We further adjusted the event rate to address under-reporting of a) CINV rates (vs. 49.2% for aprepitant in AC in a clinical trial [Warr 2005]) and b) acute-care use, projected at 17-50% at sites external to the dataset. To compare the resulting adjusted event rate to the NEPA study, we conducted 10,000 Monte Carlo simulations, using random probabilities from 5.2-8.7% for Explorys patients, and from 0-2% for NEPA patients to address potential reporting variability, despite the trial including daily patient diaries. Analysis of data was limited to the first two cycles, the median duration in the NEPA trial. Results: In the NEPA trial, 402 patients received ≥1 cycle; 391 completed two cycles. Nine patients had IP admissions; none involved CINV. Five patients had 6 total ED visits; one met criteria for involving CINV; the resulting rate of acute care rate involving CINV was 0.25 per 100 patients. For other antiemetics, 2598 patients received AC (excluding NEPA prophylaxis). Among 1206 age-matched to the NEPA trial, 15 patients had acute-care events in the first 2 cycles, (1.24 per 100 patients), an odds ratio of 1:5.1 (CI 0.7-38.5) in favor of NEPA. After adjusting via the simulation, the odds ratio was 1:8.3 (CI: 2.43-24.21) in favor of NEPA. Conclusions: Comparing CINV-related acute care seen in a large prospective trial relative to real-world evidence in patients with breast cancer treated with AC, <1% of patients receiving NEPA prophylaxis required acute care for CINV; the CINV-related acute-care risks seen with other antiemetic prophylaxis were 5 times (unadjusted) to 8 times (adjusted) the levels for NEPA. A similar comparison using only real world data should be conducted as data permit. Citation Format: Lee Schwartzberg, Kathryn J Ruddy, Rudolph M Navari, Thomas W LeBlanc, Rebecca Clark-Snow, Rita Wickham, Gary Binder, William L. Bailey, Ravi Potluri, Luke M Schmerold, Eros Papademetriou, Eric J Roeland. Avoidable acute care involving chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer receiving anthracycline + cyclophosphamide (AC) with NEPA prophylaxis relative to other antiemetics: An external control arm analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-07.

PURPOSE: After ASCO and National Comprehensive Cancer Network guideline recommendations for triple antiemetic prophylaxis for carboplatin area under the curve (AUC) ≥ 4, and the publication of studies documenting avoidable acute care after chemotherapy involving nausea and vomiting (NV) and other toxicities, we studied clinician adherence to the guideline change and assessed avoidable acute-care use. METHODS: Using a large electronic health record database, we evaluated antiemetic prophylaxis as recommended in the guidelines and post-chemotherapy avoidable acute-care use (defined as involving any of NV or 8 other toxicities) for patients initiating carboplatin or other chemotherapy from October 2012 to August 2018. RESULTS: We identified 11,554 carboplatin courses. After the guideline change adding neurokinin-1 receptor antagonists (RAs) for carboplatin AUC ≥ 4, its use rose to 20% of courses from the prior average of 16%; virtually all courses also included a 5-HT3 RA plus dexamethasone. We found avoidable acute care in 23% of courses; one quarter of these events were associated with NV. Acute care rates after carboplatin mirrored those after other highly emetogenic chemotherapy or oxaliplatin and exceeded those after other chemotherapy regimens. The > 80% shortfall in adherence may have been caused by low awareness or acceptance of the guideline change and/or by poor awareness of avoidable acute-care use after carboplatin. CONCLUSION: Neurokinin-1 RA prophylaxis for carboplatin AUC ≥ 4 remains low and largely unchanged despite National Comprehensive Cancer Network and ASCO 2017 recommendations for inclusion. NV and avoidable acute care involving NV seen after carboplatin were consistent with other highly emetogenic chemotherapy. Clinician action is required to remediate incomplete prophylaxis and to no longer place patient outcomes, resources for cancer treatment, and clinician reimbursement at risk.

112 Background: In the US, the CMS OP-35 oncology outcome measure deems 30-day post-chemotherapy acute care involving nausea and emesis (NV) or 8 other toxicities as avoidable, with studies showing 15% of > 2500 patients receiving anthracycline + cyclophosphamide (AC)-based chemotherapy had avoidable acute care, of which 32% involved NV. Our aim was to evaluate resource use (emergency department [ED] visits, inpatient admissions [IP], or hydration) in a prospective trial of women with breast cancer who received combination netupitant/palonosetron (NEPA) + dexamethasone (DEX) for CINV prophylaxis for AC-based chemotherapy. Methods: Women initiating AC received oral or IV NEPA + DEX. Pre-specified endpoints included safety, complete response, acute care (ED/IP), unplanned IV hydrations (as determined by investigator), days of CINV, and ≥3 days of CINV. We defined CINV as emesis or rescue drug use up to 5 days after AC, and defined concomitant ED/IP or hydrations in the same period as CINV-related. We limited our analysis to the first 2 cycles, the median duration in the NEPA study. Results: 402 patients received ≥1 cycle of AC and 391 completed 2 cycles. Nine patients had IP (none CINV-related), and 5 patients had a total of 6 ED visits (1 CINV-related). Three patients had a CINV-related unplanned hydration. Patients had ≥1 day of CINV in 172 of 793 cycles (21.7%); of these, the majority had symptom duration for 1-2 days, while 78 (9.8%) had ≥3 days of CINV in a cycle. Conclusions: In this prospective CINV prophylaxis study in women receiving AC chemotherapy, < 1% of women receiving NEPA + DEX required acute care for CINV and < 1% required unplanned hydrations for CINV. These rates are below previously reported CINV-related acute care rates for AC suggesting NEPA may help avoid CINV-related acute care. Clinical trial information: NCT03403712.

Abstract Background: Palliative care specialists provide supportive care for patients with hematologic diseases. However, the degree of engagement by palliative care physicians may be limited by the views of both palliative care physicians and hematologists. Prior studies have surveyed hematologists to identify barriers to delivery of palliative care, however palliative care physician views are unclear. This study aimed to examine views of palliative care physicians toward hematology. Methods: A survey was mailed to a random sample of the AAHPM physician contact list in 2017. Items focused on perceptions of their understanding of hematologic diseases, comfort providing care, opinions regarding palliative care and hospice involvement, and beliefs about hematologists. Anonymized responses were assessed on a Likert scale. Statistical testing was based on logistic regression models with generalized estimating equations to account for correlated data within respondents. Results: 538 of 1000 surveys were completed. 51.9% of respondents were male. Community (37.2%), academic (36.7%) and hospice (26.2%) physicians were represented. Respondents were likelier to believe they understand the trajectories of lymphoma and myeloma than leukemia or patients undergoing hematopoietic stem cell transplantation (HSCT) (p < 0.001). They were more comfortable discussing prognosis (p =< 0.001) and managing symptoms (p < 0.001) in lymphoma and myeloma than leukemia and HSCT. They were likelier to believe that hematologists' perceptions of palliative care physicians limit collaboration rather than their own views of hematologists (p < 0.001). 80.2% agreed that hospice referrals are not made early enough. Conclusions: Palliative care physicians' understanding of trajectories and comfort caring for patients varies by hematologic disease. They perceive that hematologists' perceptions are a larger barrier than their own and hospice referrals are delayed. These results provide insights into opportunities for better collaboration with hematologists. Disclosures No relevant conflicts of interest to declare.

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. Recent advances have resulted in an expansion of treatment options for AML, especially concerning targeted therapies and low-intensity regimens. This portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML focuses on the management of AML and provides recommendations on the workup, diagnostic evaluation and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients.

e23108 Background: ASCO antiemetic guidelines recommend upfront triple prophylaxis (NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC). Physicians exhibit high variation in HEC guideline adherence, principally involving inclusion of NK1 RA. Whether adherence is associated with selection of the specific 5HT3 RA agent remains inadequately studied. Methods: In the IBM Explorys electronic health record database, we used procedure and diagnosis codes to identify HEC courses and related nausea/vomiting (NV) from 2012 to 2018. We defined HEC guideline adherence as triple prophylaxis at chemotherapy initiation. We assigned HEC courses for ≥ 7 day cycles of cisplatin or anthracycline + cyclophosphamide (AC), or carboplatin (≥ 14 day cycles as a proxy for AUC ≥ 4) to prescribing oncologists based on encounter frequency. We categorized 5HT3 RA use of each physician treating ≥ 5 HEC courses based on their most commonly used 5HT3 and performed descriptive statistics. Results: Of 12,262 HEC courses, 57% involved physicians having greater use of ondansetron (OND) (mean OND to palonosetron (PALO) ratio of 3.9:1). These courses had lower guideline adherence (due to NK1 RA omission) and higher rates of NV for combined HEC, AC, and carboplatin. NV rates for cisplatin did not vary by 5HT3 agent used. Courses involving physicians with greater PALO use (mean OND:PALO ratio of 0.2:1) had superior adherence and NV rates, despite involving a slightly higher risk population (younger and/or female). Conclusions: According to HEC antiemetic guidelines, NK1 RA use should occur independent of 5HT3 RA agent selection. However, we observed less NK1 RA use where OND was preferred, which may have caused the observed higher rates of NV with OND. Further evaluation should assess whether pharmacy cost minimization is a driver of both OND preference and NK1 omission in HEC. [Table: see text]

Abstract Background: In order to improve care and reduce costs of cancer treatment, attention has focused on reducing inpatient (IP) and emergency room (ED) utilization. The US Centers for Medicare and Medicaid Services (CMS) recently implemented an oncology outcome measure (OP-35) to assess the quality of care and determine outpatient hospital payment. It assesses 30-day post-chemotherapy rates of IP or ED events deemed “potentially avoidable” by CMS due to association with any of 10 CMS-defined toxicities: anemia, dehydration, diarrhea, fever, nausea, emesis, neutropenia, pain, pneumonia, or sepsis. Although CMS found that 20% of chemotherapy treatment resulted in such events, event rates with highly emetogenic chemotherapy (HEC) are understudied, particularly for breast cancer (bCA) patients treated with anthracycline + cyclophosphamide (AC), carboplatin, or cisplatin. Methods: In a large electronic health record database focused on US integrated delivery networks, HEC courses of therapy were identified from 4Q 2012 to 3Q 2017. IP/ED events within 30 days of chemotherapy administration were considered related to the OP-35 measure if they included a diagnosis code of any of the ten OP-35 toxicities, per CMS' definitions. HEC chemotherapy use, IP/ED events, bCA diagnosis, and toxicities were identified by ICD-9, ICD-10, and procedural codes. Subgroups were evaluated for 3 common HECs: AC, carboplatin (&gt;14 days apart, as a proxy for AUC ≥4), and cisplatin. Results: 4128 courses of HEC in bCA were identified. Of these, 2304 involved AC (median 4 cycles), 1721 involved carboplatin (median 6 cycles), and 103 involved cisplatin (median 4 cycles), with median ages of 55, 59, and 64, respectively. 30-day IP/ED events were seen in 25% of these HEC bCA courses (22%, 30% and 23% for AC, carboplatin, and cisplatin, respectively). The 10 CMS-defined toxicities were associated with an IP/ED event for 73%, 72%, and 76% of events for these AC, carboplatin, and cisplatin courses respectively, confirming that these are principal contributors to 30-day IP/ED use for patients receiving HEC in bCA. The top five that were most commonly associated with IP/ED for bCA for patients receiving AC, carboplatin, or cisplatin were pain 53%/49%/63%, anemia 51%/51%/38%, fever 48%/31%/38%, neutropenia 46%/27%/31%, and nausea/emesis 30%/40%/25%; patients may have had ≥1 toxicity associated with each IP/ED event. The IP/ED rate may be understated because some events, particularly ED, may occur out of the network the EHR data covers. Conclusion: One quarter of patients receiving AC, carboplatin, or cisplatin for bCA visit the ED or are hospitalized within 30 days of at least one of their chemotherapy administrations. Most events involved ≥1 of 10 toxicities deemed avoidable causes of hospitalization by CMS and now tracked as an oncology outcome measure. Relative to patients receiving AC, acute care rates for patients receiving carboplatin were lower for fever and neutropenia and higher for nausea/emesis, perhaps because the study period largely precedes the 2017 addition of carboplatin AUC ≥4 to national guidelines as HEC requiring triplet antiemetic prophylaxis. Toxicity prevention and symptom monitoring are crucial to reduce acute care needs. Citation Format: Ruddy KJ, Roeland EJ, LeBlanc TW, Binder G, Sebastiani S, Potluri R, Schmerold LM, Papademetriou E, Navari RM. Avoidable acute care use associated with nausea and emesis among patients receiving AC, carboplatin, or cisplatin for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-05.

651 Background: Oxaliplatin (OX), used primarily in gastrointestinal cancers, is considered moderately emetogenic while multiple guidelines classify carboplatin and cisplatin as highly emetogenic chemotherapy (HEC). The new oncology outcome measure (OP-35) from the US Centers for Medicare and Medicaid Services (CMS) deems 30-day post-chemotherapy inpatient (IP) and emergency room (ED) events “potentially avoidable” if involving nausea or emesis (NV) or any of eight other toxicities. We lack data comparing avoidable IP/ED and NV events for OX relative to platinums classified as HEC. Methods: We assessed OX, cisplatin, and carboplatin courses of therapy from 4Q 2012 to 1Q 2018 using the IBM Watson Explorys database. We identified IP/ED and OP-35 toxicities (anemia, dehydration, diarrhea, fever, NV, neutropenia, pain, pneumonia, or sepsis) by diagnosis and procedure codes, and stratified results by sex and age < 70 (median age at diagnosis for colorectal cancer). An IP/ED event could involve ≥ 1 OP-35 toxicity. We also evaluated a FOLFIRINOX subgroup (receiving irinotecan ≤ 3 days after OX). Results: In sum, we identified 4,231 OX courses (382 FOLFIRINOX) (Table). OP-35 toxicities occurred in 75% of IP/ED events; of these, 34% OX and 42% FOLFIRINOX involved NV. Rates of IP/ED, IP/ED OP-35-defined toxicity, and NV after OX were consistent with cisplatin and carboplatin. Among patients receiving OX, women age < 70 (n = 1388) had higher NV rates vs. others (p < 0.001). Conclusions: Roughly one-third of patients receiving OX experienced IP/ED events ≤ 30 days post chemotherapy. Most involved ≥ 1 of 10 OP-35 toxicities, meeting CMS’ criteria as potentially avoidable acute care. OX IP/ED rates and NV rates were similar to other platinums and were worse among women age < 70, suggesting more aggressive antiemetic prophylaxis should be evaluated. [Table: see text]

95 Background: Palliative care (PC) specialists provide supportive care for patients with hematologic diseases (HD). However, the degree of engagement by PC physicians may be limited by the views of both PC physicians & hematologists. Prior studies have surveyed hematologists to identify barriers to delivery of PC, however PC physician views are unclear. This study aimed to examine views of PC physicians toward hematology. Methods: A survey was mailed to a random sample of the AAHPM physician contact list in 2017. Items focused on perceptions of their understanding of HD, comfort providing care, opinions regarding PC & hospice involvement, & beliefs about hematologists. Anonymized responses were assessed on a Likert scale. Statistical testing was based on logistic regression models with generalized estimating equations to account for correlated data within respondents. Results: 538 of 1000 surveys were completed. 51.9% of respondents were male. Community (37.2%), academic (36.7%) & hospice (26.2%) physicians were represented. Respondents were likelier to believe they understand the trajectories of lymphoma & myeloma than leukemia or patients undergoing hematopoietic stem cell transplantation (HSCT) (p < 0.001). They were more comfortable discussing prognosis (p < 0.001) & managing symptoms (p < 0.001) in lymphoma & myeloma than leukemia & HSCT. They were likelier to believe that hematologists’ perceptions of PC physicians limit collaboration rather than their own views of hematologists (p < 0.001). 80.2% agreed that hospice referrals are not made early enough. Conclusions: PC physicians’ understanding of trajectories & comfort caring for patients varies by hematologic disease. They perceive that hematologists’ perceptions are a larger barrier than their own & hospice referrals are delayed. These results provide insights into opportunities for better collaboration with hematologists.

74 Background: U.S. National Antiemetic Guidelines recommend upfront triple prophylaxis (NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC), including carboplatin AUC ≥ 4 per 2017 guidelines. While existing data show gaps in guideline compliance, variation between individual physicians is less studied, and a realistic target compliance rate remains unknown. Methods: In a large electronic health record database (IBM Explorys), we identified HEC courses of therapy initiated from 2012 to 2017. Guideline compliance was defined as triple prophylaxis at chemotherapy initiation. Patient courses for ≥ 7 day cycles of cisplatin or anthracycline + cyclophosphamide (AC), or carboplatin (≥ 14 day cycles as a proxy for AUC ≥ 4) were ascribed to oncologists based on encounter frequency. We then ranked physicians treating ≥ 5 HEC courses and evaluated guideline compliance and individual physician variation. Results: In total, 10,074 HEC courses were identified and attributed to 451 unique physicians. Overall antiemetic guideline compliance with cisplatin and AC averaged 68% and 81% respectively. When ranked by compliance, the top 20% of physicians were 2.5 - 1.5 times as compliant as the bottom 20% (cisplatin 100% vs 40%; AC 100% vs 67%). For cisplatin, 32% of physicians had > 90% compliance; the remaining 68% were evenly distributed from 0 - 90%. For AC, 56% of physicians had > 90% compliance, and another 14% had 80 - 90%; the remaining 30% were evenly distributed. For carboplatin, 62% of physicians had ≤ 10% compliance, and another 17% had 11 - 20%; however, the majority of these data preceded guideline inclusion of carboplatin AUC ≥ 4 as HEC. Rates were independent of course volume per physician. Conclusions: Considerable physician-level variation exists in triple antiemetic prophylaxis guideline adherence for HEC. Hundreds of physicians had > 90% compliance with guidelines, suggesting 90% is a realistic target. However, the majority exhibited substantial gaps in NK1 RA use in HEC, placing patients unnecessarily at risk for CINV. Interventions are needed to bolster triple antiemetic prophylaxis in HEC, perhaps especially for carboplatin.