Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study

BACKGROUND: 1(st) generation 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), and palonosetron, a 2(nd) generation 5-HT(3) RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT(3) RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. METHODS: Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT(3) RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. RESULTS: Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT(3) RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT(3) RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT(3) RAs, the palonosetron groups incurred 22%-51% fewer 5-HT(3) RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT(3) RA group (p < 0.05). CONCLUSIONS: Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT(3) RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz

Aim: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. Methods: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. Results: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). Conclusion: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.Sandoz Inc., Princeton, NJ, USAOpen access article.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Incremental cost of treating hypertension in the United States

The objective of this study was to determine incremental direct cost of treating hypertension in the U.S. population using an incremental cost approach. Analysis of the 2001 Medical Expenditure Panel Survey (MEPS), a national probability survey containing data for healthcare utilization, expenditures, payment sources, and insurance coverage for the civilian non-institutionalized U.S. population, was conducted. Hypertensive patients were identified as those with a medical diagnosis for hypertension using International Classification of Diseases codes, patients who consumed hypertension related medical care services or treatments during 2001, patients who self-reported being diagnosed as having hypertension by their physician and patients who were prescribed an anti-hypertensive medication. Incremental cost of treating hypertension was estimated through least squares regression adjusting for age, gender, race, education, and co-morbidities using the Charlson co-morbidity index. Sample data were projected to the U.S. population and 95 percent confidence limits for estimates were calculated using the Taylor expansion method. Sample estimates projected to the population indicated that approximately 17.4 percent of individuals aged 18 years and above in the United States had hypertension. Total incremental annual direct costs for hypertension patients were estimated to be more than $54.0 billion after adjusting for demographics and co-morbidities, with mean incremental annual per capita direct cost for a hypertensive individual being$1,131. Resource utilization was significantly higher among hypertensive patients (p\u3c 0.0001) in each of several medical care services examined including prescription medicines, inpatient visits, outpatient visits, emergency room visits, office-based medical provider visits, home health visits, and other medical expenses as compared to non-hypertensive patients. Prescription medicines, inpatient visits, and outpatient visits constituted more than 90 percent of the overall incremental cost of treating hypertension. With hypertension affecting approximately 17.4 percent of the population in the year 2001 and incremental direct medical costs estimated at nearly $55.0 billion for the year 2001, hypertension costs represent a significant economic burden

Cost-minimization analysis for biosimilar pegfilgrastim in the prophylaxis of chemotherapy induced (febrile) neutropenia and expanded access based on budget neutral basis.

6645 Background: Pegfilgrastim (pegfil) injection is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Assuming biosimilarity of biosim-pegfil and pegfil in the prevention of febrile neutropenia, we estimated cost minimization of conversion from pegfil to biosim-pegfil and subsequent potential expanded access due to cost savings. Methods: A cost minimization model was conducted based on a hypothetical panel of 20,000 patients using average selling price (ASP) for one chemotherapy cycle. ASP was obtained from 1Q 2019 payment allowance limits. The simulation included two steps: 1) cost minimization was calculated per cycle (biosim-pegfil and pegfil is administered 1 dose per cycle) when patients were converted to biosim-pegfil from pegfil on ratio of 10% to 100% at 10% intervals and at a discount from 15% to 35% at 5% intervals, and 2) expanded access to biosim-pegfil was calculated based on budget neutrality. Since pegfil has two forms of availability (Neulasta and Neulasta-Onpro) with the same price, results were to either conversion scenario. Results: Per-cycle per-patient cost minimization from converting pegfil to biosim-pegfil ranged from $702.27 (15$1,638.63 (35% discount). For 20,000 patients, this yields savings of over $14 million (15$32 million (35% discount) at 100% conversion rate. When half the patients were converted to biosim-pegfil, savings could range from &gt; $7 million (15$16 million (35% discount). With 100% conversion rate and 15% discount, 3,529 additional patients could be treated with the savings generated. At 50% conversion rate, cost savings could be applied to another 1,765 patients with 15% discount, 3,333 patients with 25% discount, and 5,385 patients with 35% discount, respectively. Conclusions: Conversion from pegfil to biosim-pegfil can lead to potential cost savings and these savings can be applied to offer increased access to supportive care with biosim-pegfil for patients receiving chemotherapy on a budget-neutral basis. For payers with larger populations, savings can be substantial. More studies are warranted to evaluate such potential cost savings due to use of biosim-pegfil over reference pegfil. </jats:p

Palonosetron Versus Other 5-HT3-Receptor Antagonists for the Prevention of Chemotherapy Induced Nausea and Vomiting In Patients with Hematologic Malignancies Treated In A Hospital Outpatient Setting

Abstract Abstract 2567 Objective: This analysis explored the risk of uncontrolled chemotherapy induced nausea and vomiting (CINV) associated with initiation of palonosetron versus other 5-hydroxy tryptamine3-receptor antagonists (5-HT3-RAs) among patients with leukemia and/or lymphoma receiving chemotherapy (CT) [highly emetogenic chemotherapy, moderately emetogenic chemotherapy, low emetogenic chemotherapy, or minimal emetogenic chemotherapy] treatment in a hospital outpatient setting. Methods: Patients diagnosed with any leukemia and/or lymphoma [identified through appropriate International Classification of Diseases, Clinical Modification, 9th Revision codes (ICD-9-CM)] initiating any CT and anti-emetic prophylaxis with palonosetron (Group 1) or other 5-HT3-RAs (Group 2) for the first time (index date) between April 1, 2007 and March 31, 2009 were identified from the Premier Perspective comparative research database. Other inclusion criteria were patients aged ≥ 18 years, no prior evidence of nausea and vomiting or a hospital charge for a CT or anti-emetic medication in the 6-month pre-index date period, and at least one CINV event in the post-index date follow-up study period. Patients also needed to have at least 36 consecutive months of hospital data submissions. Patients were followed through eight CT cycles or six months post index date, whichever occurred first. The unit of analysis was a CT cycle. Group 1 and Group 2 patients were matched on type of CT, specific CT cycle, and leukemia/lymphoma diagnosis using propensity scoring. A negative binomial distribution generalized linear multivariate regression model estimating the number of CINV events (identified through either ICD-9-CM codes for nausea and/or vomiting and volume depletion or CINV-related rescue medications one day after CT administration) in the follow-up period between the matched groups was developed after adjusting for other significant differences in demographic and clinical variables at index date (baseline) including age, gender, patient weight, payor type, patient race, CT cycle duration, and CT duration in days. Results: Of 1,256 identified patients, 234 initiated with palonosetron (Group 1; 18.6%). Group 1 patients were significantly younger [60.8 (SD: 17.9) vs. 64.4 (14.8) years; p=0.0045], comprised more females [49.6% vs. 43.2%; p&lt;0.0001], received more emetogenic CT (high and moderate) [88.5% vs. 77.1%; p&lt;0.0001], and less African Americans [9.4% vs. 12.7%]. Group 1 also had a lower percentage of patients with leukemia [9.0% vs. 17.6%; p&lt;0.0001], and more patients with lymphoma [82.5% vs. 63.1%; p&lt;0.0001]. In the follow-up period, the unadjusted number of CINV events per patient per CT cycle for Group1 patients was significantly lower versus Group 2 patients (3.4 vs. 4.3 CINV events per patient per CT cycle; p&lt;0.0001). The regression model predicted a 32% reduction in the total CINV events per patient per CT cycle for Group 1 patients versus Group 2 patients; p=0.0003. Other significant variable results from the model included patients aged &lt; 65 years had a 39.9% lower risk of total CINV events per patient per CT cycle versus patients aged ≥ 65 years; p=0.0009 and commercially insured patients had a 44.2% lower risk of total CINV events per patient per CT cycle versus traditional Medicare patients; p=0.0003. Conclusion: In this hospital outpatient retrospective database analysis, patients with hematologic malignancies initiated and maintained on palonosetron were more likely to experience a significantly lower rate of CINV events per patient per CT cycle versus those initiated on other 5-HT3-RAs. Disclosures: Craver: Eisai, Inc.: Research Funding. Gayle:Eisai, Inc.: Research Funding. Balu:Eisai, Inc.: Employment. Buchner:Eisai, Inc.: Employment. Off Label Use: The study was on hematology patients on all chemotherapy types (high, moderate, low, and minimal) even though the drug (palonosetron) is approved for highly emetogenic chemotherapy and moderately emetogenic chemotherapy in the United States. </jats:sec

Impact of 5-Hydroxytryptamine-3 Receptor Antagonist Step Therapy on Severe Chemotherapy-Induced Nausea and Vomiting Events in Patients with Lymphoma

Abstract Abstract 3137 Introduction: Older 5-hydroxytryptamine3 receptor antagonists (5-HT-3 RA), e.g., ondansetron and the more recent palonosetron are indicated for prevention of chemotherapy (CT) induced nausea and vomiting (CINV). Step therapy is a policy that encourages the use of generic 5-HT3 RAs, reserving prophylaxis with palonosetron as second-line therapy as means to containing costs. Objective: To evaluate potential impact of step therapy policy on risk of severe CINV events among patients (pts) with lymphoma who used ondansetron, granisetron, or dolasetron and later switched to palonosetron versus pts who were initiated and maintained on palonosetron throughout multiple CT cycles. Methods: Pts initially diagnosed with lymphoma during 2005–2009 were selected from PharMetrics claims dataset if enrolled for ≥6 months before first lymphoma diagnosis and received cyclophosphamide based CT and 5-HT-3 RA prophylaxis. Pts were followed (FUP) for 6 months from 1st CT date. Based on 5-HT-3 RA used at FUP, pts were grouped into those initiated and maintained on palonosetron throughout versus those initiated with an earlier 5-HT-3 RA and later switched to palonosetron. Outcomes included risk of severe CINV (using ICD-9 codes) associated with hospitalizations or ER admissions, as well as days with severe CINV. Logistic and Poisson regression models were used to compare risk and days with severe CINV, adjusting for cyclophosphamide dose received during the 6-month FUP, age, gender, Charlson Comorbidity Index (CCI), and the year of lymphoma diagnosis. Results: A total of 953 patients who used palonosetron throughout the FUP (palonosetron group) and 113 patients who switched from an older 5-HT-3 RA to palonosetron (switched group) were analyzed. The average (mean±SD) age at lymphoma diagnosis was 60.3±13.8 years, CCI was 0.47±0.97, number of cyclophosphamide treatment days was 5.6±1.93, and cyclophosphamide dose (mg/m2) per CT cycle was 930±676. Palonosetron group was significantly older (60.8 vs. 55.9 years, p=0.0006). There were no significant differences (NS) between the two groups in gender, CCI, or year of lymphoma diagnosis. Palonosetron group had significantly fewer 5-HT-3 RA prescription claims (4.81 vs. 7.72, p&lt;0.0001). There was NS difference between the two groups in cyclophosphamide dose [palonosetron: 937 vs. switched: 871], p&gt;0.05), although palonosetron group had significantly fewer CT treatment days (5.5 vs. 6.3, p=0.0135). Proportion of patients with ≥1 severe CINV events was significantly higher in the switched group (15.9% vs. 6.3%, p=0.0002). Switched group also had significantly more claims and days with severe CINV (2.4 vs. 0.6 in CINV claims, p=0.0001; 0.4 vs. 0.1 in CINV days, p=0.0002). Logistic regression controlling for covariates showed the palonosetron group to experience significantly lower risk of approximately 70% for hospital/ER related CINV than the switched group (Odds Ratio=0.311, p=0.0001), while older age significantly increased such an outcome. Poisson regression with number of days with severe CINV as the outcome variable found that palonosetron group had nearly 75% fewer hospital/ER related CINV days than the switched group (p=0.0024). Conclusion: Patients with lymphoma initiated and maintained on palonosetron throughout the CT cycles were at significantly lower risk and experienced fewer days with severe CINV as compared to those who were initiated on an older 5-HT-3 RA and later on switched to palonosetron. Further studies of the impact of step therapy policy with regard to first 5-HT3-RA therapy in patients with lymphoma are needed in order to assess the related economic and humanistic burden. Disclosures: Hatoum: Eisai: Consultancy, Research Funding. Lin:Eisai: Consultancy. Balu:Eisai: Employment. </jats:sec