Navari, Rudolph M.

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.

11595 Background: In 2017, NCCN (2/2017) and ASCO (8/2017) each amended antiemetic guidelines to classify carboplatin AUC ≥4 as highly emetogenic chemotherapy (HEC), recommending upfront triple prophylaxis with an NK1 receptor antagonist (RA) + 5HT3 RA + dexamethasone. Physician concordance with the new recommendations, and the consequences for avoidable post-chemotherapy acute care, merit study. Methods: In a large electronic health record database (IBM Explorys), we identified carboplatin courses of therapy (≥14-day cycles as a proxy for AUC ≥4) and courses with ≥7-day cycles of other HEC and non-HEC therapy from 4Q 2012 through August 2018. Guideline concordance, defined as triple prophylaxis at HEC initiation, was evaluated. We also assessed 30-day post-chemotherapy acute care (inpatient or emergency department) associated with nausea or vomiting (NV) or eight other toxicities deemed avoidable in the US Centers for Medicare & Medicaid’s new oncology outcome measure OP-35. Results: 11,554 carboplatin courses were identified. Before the guideline change, rates of upfront triple prophylaxis grew from 14% in 2013 to 16% in mid-2017. Rates then rose to 26% by 1Q 2018 before dropping to 21% by 3Q 2018; quarterly rates averaged 20% (range 15%-26%) following the guideline change. In 31% of carboplatin courses we noted 30-day acute care use, of which 75% involved ≥1 of the ten OP-35 toxicities. NV (with or without acute care use) was reported in 24% of courses, and 27% of total OP-35 acute care events involved NV. Rates for NV, and for OP-35-related and NV-related acute care after carboplatin, were similar to rates after other HEC chemotherapy, and higher than rates after other non-HEC IV chemotherapy or oral HEC/MEC agents. Conclusions: Use of upfront triple antiemetic prophylaxis has increased only marginally for carboplatin AUC ≥ 4 since its 2017 re-classification as HEC in national guidelines, perhaps due to low awareness of the change. Patients receiving carboplatin had similar rates of NV and related 30-day acute care events as seen for other HEC, confirming that the new HEC definition fits clinical experience. More triple prophylaxis use is needed to reduce NV and NV-related avoidable acute care seen with carboplatin AUC ≥ 4.

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.

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]

Background: Avoiding acute care services can improve cancer care and reduce cost. The US Centers for Medicare and Medicaid Services’ (CMS) new oncology outcome measure (OP-35) defines 30-day post-chemotherapy inpatient (IP) and/or emergency department (ED) events (IP/ED) as “potentially avoidable” if involving any of 10 toxicities, including nausea or vomiting (NV). Evidence demonstrates meaningful gaps in oncologists’ adherence to antiemetic prophylaxis guidelines for highly emetogenic chemotherapy (HEC), and that NV-related IP use costs >$10,000; yet the incidence of avoidable acute care events involving NV is not well studied. Methods: We assessed chemotherapy courses using IBM Explorys electronic health records (4Q 2012–1Q 2018). We identified rates of IP/ED ≤30 days post-chemotherapy, and OP-35 toxicities (NV, anemia, dehydration, diarrhea, fever, neutropenia, pain, pneumonia, or sepsis) by ICD-9, ICD-10, procedure codes, and CMS criteria. We evaluated cisplatin, anthracycline + cyclophosphamide (AC), carboplatin (>14 days apart, as a proxy for AUC ≥4), oxaliplatin (OX), and other non-HEC chemotherapy. We assessed guideline adherence, defined as triple prophylaxis (NK1 RA + 5HT3 RA +dexamethasone) rates at HEC initiation. Results: In 17,609 HEC and 56,624 non-HEC courses, we observed 30-day IP/ED utilization in 29% and 19% of courses, respectively (Table 1). For HEC, 76% of IP/ED use involved ≥1 of the 10 CMS toxicities, most often anemia (42%), pain (41%), dehydration (24%), and NV (24%). Rates of all-cause IP/ED, IP/ED with OP-35 toxicity, and NV-related IP/ED were consistent for HEC and OX. Gaps in triple prophylaxis were common in HEC. Conclusion: Roughly one-third of patients receiving HEC or OX experienced IP/ED events ≤30 days after chemotherapy. Three-quarters of IP/ED events involved ≥1 of 10 OP-35 toxicities linked by CMS to potentially avoidable acute care; of these, one-third involved NV. NV-associated acute care use is considerable, costly, and potentially avoidable with better adherence to antiemesis guidelines.

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]

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.

112 Background: Reducing hospitalizations for chemotherapy-related toxicities represents an opportunity to improve both the quality and cost of cancer treatment. Nausea and vomiting (NV) account for almost 10% of “avoidable” toxicity-related post-chemotherapy hospitalizations (2016 Medicare data). We sought to evaluate the event cost of NV-related hospitalizations among patients with cancer from a US payer perspective. Methods: From a large US claims database (Truven MarketScan), we identified hospitalizations with NV as the primary diagnosis and cancer as a secondary diagnosis (01/2011-06/2017). This method increases specificity for NV as the principal hospitalization factor, while underreporting the prevalence of NV as a contributory factor. To determine event costs, we evaluated hospital and other reimbursement during the hospitalization. To explore subgroup differences, we stratified results by tumor type, payer type, admission route, receipt of highly emetogenic chemotherapy (HEC; 2017 definition includes carboplatin AUC ≥4) and antiemetic prophylaxis. We adjusted all costs to 2017 US dollars. Results: Among 918,192 hospitalizations involving cancer, we identified 80,995 with both NV and a cancer diagnosis code. Of these, 5,293 had NV as the primary diagnosis and 62 lacked cost data. Patients (mean age = 57.7±16.2) were 67% female. Median hospital length of stay was 4 days and mean cost per hospitalization was $15,085. Non-Medicare admissions (82%) had a higher mean cost vs. Medicare ($15,737 vs. $12,111, p < 0.01). We found < $1,000 difference between the highest and lowest cost per hospitalization among the 6 most common tumor types. We found the 65% of patients with a chemotherapy claim ≤30 days prior to hospitalization had costs of $13,882 per event. Among the 45% of chemotherapies that were HEC, > 50% lacked an NK1 receptor antagonist as prophylaxis. Conclusions: The average cost of NV-related hospitalizations among patients with cancer exceeds $15,000 per event, highlighting the need to effectively address this symptom. Roughly half the hospitalizations involved HEC, with over half of those patients not receiving guideline-based antiemetic prophylaxis.