Aprepitant Arm Research Articles

Health-Related Quality of Life and Economic Analysis of Olanzapine Versus Aprepitant in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Malaysia

ObjectivesOlanzapine has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) after highly emetogenic chemotherapy (HEC); however, there is limited work on the impact of CINV on health-related quality of life (HRQoL) and the comparative cost-effectiveness of CINV prophylaxis in the Malaysian context. Therefore, this study was conducted to determine the HRQoL using EQ-5D-5L and the cost-effectiveness of olanzapine compared with aprepitant for CINV prophylaxis in Malaysia using data from a local study. MethodsFifty-nine chemo-naive patients receiving either olanzapine or aprepitant were randomly recruited and completed the EQ-5D-5L before and day 5 after HEC. HRQoL utility scores were analyzed according to the Malaysian valuation set. The economic evaluation was conducted from a healthcare payer perspective with a 5-day time horizon. Quality-adjusted life days (QALD) and the rate of successfully treated patients were used to measure health effects. The incremental cost-effectiveness ratio is assessed as the mean difference between groups’ costs per mean difference in health effects. A one-way sensitivity analysis was performed to assess variations that might affect outcomes. ResultsAprepitant and olanzapine arms’ patients had comparable baseline mean HRQoL utility scores of 0.920 (SD = 0.097) and 0.930 (SD = 0.117), respectively; however, on day 5, a significant difference (P value = .006) was observed with mean score of 0.778 (SD = 0.168) for aprepitant and 0.889 (SD = 0.133) for olanzapine. The cost per successfully treated patient in the aprepitant arm was 60 times greater than in the olanzapine arm (Malaysian Ringgit [MYR] 927 vs MYR 14.83). Likewise, the cost per QALD gain in the aprepitant arm was 36 times higher than in the olanzapine arm (MYR 57.05 vs MYR 1.57). Incremental cost-effectiveness ratio of MYR −937.00 (USD −200.98) per successfully treated patient and MYR −391.84 (USD −85.43) per QALD gained for olanzapine compared with the aprepitant-based regimen. ConclusionsAn olanzapine-based regimen is a cost-effective therapeutic substitution in patients receiving HEC in Malaysia.

Cost-effectiveness of single-day intravenous fosaprepitant versus three-day oral aprepitant anti-emetic regimen in pediatric patients receiving highly-emetogenic chemotherapy.

10075 Background: The non-inferiority of single-dose fosaprepitant to a three-day oral aprepitant-based anti-emetic regimen for pediatric patients receiving high emetogenic chemotherapy (HEC) has not been demonstrated. The cost-effectiveness of these regimens with respect to each other in India and the United States (US) is unknown. Methods: Individual patient data from an investigator-initiated, open-label, non-inferiority randomized control trial was used to estimate health states. The total costs and quality-adjusted life years (QALY) were calculated from the patient's perspective in India and the US. The incremental-cost utility ratio (ICUR) and net-monetary benefit (NMB) were calculated. One-way sensitivity analysis was done by varying the cost of medications, hospitalization and utility values by ±25%. Results: The fosaprepitant arm had a total QALY of 0.0116 compared to 0.0118 in the aprepitant arm. The use of fosaprepitant led to an incremental cost of $14.21 in India and a cost reduction of $193.81 in the US. The total cost of medication in the fosaprepitant arm was higher in India and lower in the US compared to the aprepitant arm. The cost of hospitalisation was lower in the fosaprepitant in both India and the US. The ICUR was -$59,974.86/QALY in India and $817,737.23/QALY in the US. The ICUR for India was located in the north-west quadrant of the cost-effectiveness plane, for the US it was located in the south-west quadrant below the willingness the pay threshold for the US. The ICUR estimate was most sensitive to the cost of fosaprepitant in India and the utility value of the complete protection health state in the US. Conclusions: Fosaprepitant was not found to be cost-effective versus aprepitant in India, comparatively it was cost-saving and cost-effective in the US. These findings highlight the necessity of region-specific considerations when evaluating the cost-effectiveness of anti-emetic regimens. [Table: see text]

Evaluation of aprepitant as an add-on therapy for prevention of chemotherapy induced nausea and vomiting in children

Background: Chemotherapy-induced nausea and vomiting (CINV), represents a common and distressing side effect associated with antineoplastic treatment in pediatric patients. Aprepitant, a selective neurokinin-1 receptor antagonist, is recommended for preventing CINV in combination with a standard antiemetic regimen in children undergoing chemotherapy. This study aimed to evaluate the effectiveness of aprepitant as an add-on therapy to the standard antiemetic regimen for the prevention of CINV in children. Methods: This randomized control study was conducted in the BSMMU, Dhaka, Bangladesh from February 2020 to October 2020. Forty-six children with malignancy undergoing chemotherapy were divided into two arms: the Aprepitant arm (23 patients receiving granisetron, dexamethasone, and aprepitant) and the control arm (23 patients receiving Granisetron and Dexamethasone). Data were analyzed using SPSS version 22.0. Results: The complete response rates for the aprepitant versus control arm during the acute and overall phase were 82% vs. 40% (p=0.003) and 65% vs. 26% (p=0.008), respectively. However, a higher percentage of patients who achieved complete response in the delayed phase was also observed, though statistically not significant (65% vs 40%, p=0.077). In the acute phase, there was a significant reduction in mild to moderate vomiting in the Aprepitant arm as compared to the control arm (p=0.01). In the overall phase, 35% of patients in the Aprepitant arm had mild to moderate vomiting as compared to 74% in the control group (p=0.027). No major adverse effects were reported by patients or caregivers. Conclusions: Adding Aprepitant to the standard antiemetic regimen was effective and safe in preventing CINV, especially in the acute phase, in pediatric patients receiving the moderately and highly emetogenic chemotherapy (HEC).

Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial

Although cough is a common and distressing symptom in patients with lung cancer, there is almost no evidence to guide treatment. Aprepitant, a centrally acting neurokinin-1 inhibitor, significantly decreased cough frequency in a pilot study. Patients with advanced lung cancer and cough lasting over 2weeks despite a cough suppressant were randomized 1:1 to aprepitant 125mg orally on day 1 and then 80mg orally on days 2 to 7 with physician's choice of antitussive; or to physician's choice of antitussive alone. Evaluation was at baseline and on days 3, 7, 9, and 12. The primary end point was subjective cough improvement on day 9, measured by the Visual Analog Scale and Manchester Cough in Lung Cancer Scale. Secondary end points included quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Lung Cancer-Specific Quality of Life Questionnaire and toxicity. Between 2017 and 2018, 128 patients were randomized. Median baseline cough duration was 90days. Mean Visual Analog Scale scores (in mm) at baseline and day 9 were 68 and 39 in the aprepitant arm and 62 and 49 in the control arm, respectively (P< .001); mean Manchester Cough in Lung Cancer Scale scores at baseline and day 9 were 33 and 23 in the aprepitant arm and 30 and 25 in the control arm, respectively (P< .001). Overall QoL was not significantly different between the two arms; however, aprepitant led to a significant improvement in the cough-specific QoL domain (P= .017). Aprepitant did not increase severe adverse events. Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects. Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in.

Combination of olanzapine and aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients.

11577 Background: Olanzapine and Aprepitant have been shown to be a safe and effective agent for the prevention of CINV. This study aims to compare Olanzapine, Aprepitant and their combination in the prevention of CINV. Methods: Prospective randomized controlled study in breast cancer patients receiving doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 chemotherapy. Female patient; age, ≥ 18; chemotherapy naïve; were included. Patients with seizure disorder, brain metastasis were excluded. Olanzapine group received Tablet Olanzapine 10 mg on day 1 to 3. Aprepitant group received Tablet. Aprepitant 125mg on day 1, 80mg on days 2-3. The combination group received Aprepitant 125mg on day 1, 80mg on days 2-3 and Olanzapine 10mg on day 1. All groups received Palnosteron 0.25mg and Dexamethasone 8mg on day 1. The primary end point of the study was complete response (CR) for nausea that is no nausea in the acute, delayed and overall periods. Secondary endpoint was CR for vomiting and no use of rescue drugs in all periods. Beginning with the first day of chemotherapy and daily through day 5, patients were asked to record daily episodes of nausea using a visual analogue scale from 0 to 10, with 0 indicating no nausea and 10 indicating a maximal level of nausea. They were asked to record daily episodes of vomiting (number and time) and the utilization of rescue therapy. Results: A total of 141 patients were evaluated and consented for the study. The median age was 47 years; range 29-80; CR for nausea in the acute period (within 24 hours) was 83%, 63.8% and 78.7% (p=0.078); for the delayed period (days 2-5) 59.6%, 55.3% and 63.8% (p=0.702); for the overall period (0-120 hours) 57.4%, 53.2% and 59.6% (p=0.817) for the Olanzapine, Aprepitant and combination arm respectively. CR for vomiting in the acute period was 91.5%, 91.5% and 97.9.7% (p=0.344); for the delayed period 74.5%, 85.1% and 97.9% (p=0.005); for the overall period 70.2%, 85.1% and 97.9% (p=0.001) for the Olanzapine, Aprepitant and combination arm respectively. There were no Grade 3/4 toxicities. Conclusions: The combination strategy shows trend towards better prevention of CINV. Clinical trial information: CTRI/2017/12/010864.

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Phase II, Open Label, Randomized Comparative Trial Of Ondansetron Alone Versus The Combination Of Ondansetron Plus Aprepitant For The Prevention Of Nausea and Vomiting In Patients (Pts) With Hematological Malignancies Receiving Regimens Containing High Dose Cytarabine

▪ BackgroundChemotherapy induced nausea and vomiting can be a significant problem for pts with acute myeloid leukemia (AML) receiving induction chemotherapy causing deterioration in quality of life. Cytarabine-containing regimens are the cornerstone for the management of AML and cytarabine is a moderate emetic risk chemotherapy agent. Combination of cytarabine with other chemotherapeutic agent can substantially worsen nausea and vomiting. Ondansetron has been used for nausea control in pts receiving chemotherapy. Aprepitant is a P/neurokinin-1 (NK1)-receptor antagonist approved for use in combination with a 5-HT3-receptor antagonist and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. We explored whether the combination of two drugs with different mechanisms of action may improve the control of nausea in pts with AML receiving cytarabine-based induction. MethodsPts with AML, high-risk MDS or CML blast phase receiving induction chemotherapy with cytarabine at a dose of ≥1 g/m2/day for at least 3 days were randomized to: Arm 1) Ondansetron 8mg IV 30 minutes before high dose cytarabine followed by ondansetron 24mg IV continuous infusion daily until 6-12 hours after the end of last chemotherapy infusion. Arm 2) Aprepitant 125mg PO plus ondansetron 8mg IV 30 minutes before high dose cytarabine followed by ondansetron 24mg IV continuous infusion daily until 6-12 hours after the end of last chemotherapy, plus aprepitant 80 mg PO daily and to continue for 1 day after last dose of chemotherapy. Pts were followed for 72 hrs post chemotherapy. A diary was used by the pts to record daily number of episodes of nausea and /or vomiting experienced during the study, as well as to record any need of extra medications for escape nausea. Complete response was defined as no emesis episodes and no use of rescue medication during the study period. Partial response was defined as ≤ 1 episode of emesis during the entire study period, no use of rescue medication during the study period, and no more than moderate nausea (NCI grade 2). ResultsForty nine pts were enrolled in each arm. Fifty seven percent were men in arm 1 and 55% men in arm 2. The median age was 53yrs (ranges, 30-68) in arm 1 and 49yrs (ranges, 21-70) arm 2. Caucasians were 83% in arm 1 and 76% in arm 2. African American and Hispanics were 10 % and 6% respectively in arm 1 and 8% and 12% in arm 2. Among the population studied 96% were diagnosed with AML in each arm. MDS 2% in arm 1 and 4% in arm 2. Fourteen percent received Idarubicin with cytarabine (Ara-C) in each arm. Twenty percent in ondansetron (OND) arm and 16% in ondansetron plus aprepitant (OND+APREP) arm receive Ara-C combined with Fludarabin. Ara-C in combination with anthracycline plus nucleoside analogues was given to 49% of pts in each arm. Ten percent in arm 1 received Ara-C with anthracycline and targeted therapy, 8% in arm 2 receive similar combination. Forty two pts on OND arm and 41 pts in the OND+APREP arm were evaluable for efficacy. Patient in the OND+APREP arms achieved higher overall response rates (complete plus partial responses) as shown in Figure 1, but the difference was not statistically significant (OND 67%, OND+APREP 80%; P= 0.11). More than 75% of pts overall were free of nausea on Days 1 and 2. On days 6 and 7 higher proportion of pts in OND+APREP arm were free from nausea than OND arm. Overall 36% of pts required rescue medications, 38% in OND arm and 34% in OND+APREP arm. Among them 14% of pts required rescue more than once; 19% in the OND arm and 10% in OND+APREP arm, as shown in Figure 2. Requirement of rescue medications on Days 2 and 3 were fewer in OND+APREP arm 7% and 5% respectively compare to 21% and 16% in the ondansetron arm (P = 0.06 and P=0.07).Most common adverse events were headache and diarrhea. Twenty percent of pts in OND arm and 19% in OND+APREP arm reported to have NCI grade 2 headache (P= 0.56). Five percent of pts in ondansetron arm and 12% in ondansetron plus aprepitant arm had grade 2 diarrhea (P=0.19). ConclusionsThe daily assessment of emesis and nausea did not show statistically significant differences between the study arms but there was a clear trend towards better responses in ondansetron plus aprepitant arm with more overall response rates and lower use of rescue medications. Further larger studies are warranted to further define the benefits of this combination of antiemetic drugs. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

A Randomized Controlled Study Evaluating The Efficacy Of Aprepitant For Highly Emetogenic Chemotherapies In Hematological Malignancies

▪ BackgroundChemotherapy induced nausea and vomiting (CINV) is a serious complication of treatments of hematological malignancies. Although 5HT3 blocker achieved modest control of acute phase CINV (<24 h of chemotherapy), prevention of delayed phase CINV (>24 h after chemotherapy) remained a challenge. Aprepitant, the oral neurokinin-1 receptor antagonist, has been revealed to have anti-emetic efficacy against both acute and delayed phase CINV in highly emetogenic therapies for solid tumors. However, its effect in the treatment of hematological malignancies has not been established. Thus we conducted a randomized controlled study to evaluate the efficacy of aprepitant in patients receiving chemotherapeutic agents for hematological malignancies. Patients and methodsWe examined the additional effect of aprepitant to conventional 5HT3 blocker-based prophylaxis for CINV in induction/consolidation of acute leukemia (n=18), platinum containing regimens for malignant lymphoma (n=18), and preparative regimens of autologous stem cell transplantation (n=5). The primary endpoint of this study was the overall complete response (CR), which was defined as no emetic episodes or no administration of rescue medications during the 10 days after the start of chemotherapies (overall period). Response rates in the acute and delayed phase were also analyzed. Secondary endpoints were the rate of (1) emesis, (2) rescue medications, and (3) significant nausea scored in visual analog scale (VAS) by patients themselves during the total study period or in acute or delayed phase. Oral food intake was also evaluated by patients. ResultsA total of 49 patients were enrolled and 41 of whom (n=22 in the aprepitant arm and n=19 in the control arm) were eligible for analysis. There was no withdrawal due to the adverse effects of aprepitant. CR rates of the aprepitant and control arms were 82% and 68% in the acute phase (p=0.47) and 82% and 58% in the delayed phase (p=0.17), respectively. Overall CR was significantly higher in the aprepitant arm (82% versus 47%, p=0.026). Emetic episodes during the entire observation period were seen at a higher rate in the control arm (9% in the aprepitant arm versus 42% in the control arm, p=0.026) and the control arm tended to have more emetic episodes than the aprepitant arm both in the acute (5% in the aprepitant arm versus 26% in the control arm, p=0.08) and delayed phases (9% in the aprepitant arm versus 37% in the control arm, p=0.057). Whilst the administration rate of salvage anti-emetic therapies was almost the same between the two arms in the early phase (14% in the aprepitant arm versus 16% in the control arm, p=1), this rate tended to be lower in the aprepitant arm in the delayed phase (18% in the aprepitant arm versus 26% in the control arm, p=0.71). In the evaluation of nausea sensation by VAS, the control arm had a trend toward higher score in the late phase. The self-assessed daily oral food intake revealed that about 50% of the patients in the aprepitant arm maintained usual amounts of food intake throughout the observation period whereas this rate dropped significantly in the control arm at day 6 (p=0.049). In the sub-group analyses to find the traits that would potentially favor aprepitant use, patients with therapies for acute leukemia had little benefit from aprepitant use (Odds ratio=0.74, p=1.0). This is probably due to moderate emetogenicity of this group, as substantiated by high CR rate in the control arm (80%). ConclusionsAprepitant confers additional anti-emetic effect to conventional 5HT3 blocker-based regimens in moderately/highly emetic chemotherapies for hematological malignancies. Disclosures:Nannya:Ono Pharmaceutical Co., Ltd: Research Funding. Kurokawa:Ono Pharmaceutical Co., Ltd: Research Funding.

Aprepitant (AP) versus dexamethasone (D) for preventing delayed emesis induced by anthracyclines plus cyclophosphamide (A+C) chemotherapy (CT) in breast cancer patients (pts): A double-blind, multicenter, randomized study.

9614 Background: A combination of AP + a 5-HT3 receptor antagonist + D and AP alone is recommended, respectively, for the prophylaxis of acute and delayed emesis induced by A+C CT in breast cancer pts. In the registrative study the role of AP in delayed emesis was not defined because prophylaxis of acute emesis was different between the two arms, and the superiority of AP on delayed emesis could be the consequence of a dependent effect on the different results achieved in acute phase. Aim of this study was to compare the efficacy of AP versus D in preventing delayed emesis in pts receiving the same prophylaxis of acute emesis. Methods: A randomized double-blind study comparing AP versus D was completed in naive breast cancer pts treated with A+C. Before CT, all pts were treated with intravenous palonosetron 0.25 mg and D 8 mg, and oral AP 125 mg. On days 2 and 3 pts randomly received D 4 mg bid or AP 80 mg qd. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) from days 2 - 5 after CT. Results: From September 2009 to July 2012, 580 pts were enrolled; 551 were fully evaluated, 273 in arm D and 278 in arm AP. Day 1 complete response rates were similar: 239/273 (87.6%) in D arm and 236/278 (84.9%) in AP arm. From day 2-5, complete response was the same with both antiemetic prophylaxes (79.5%), and all secondary endpoints (complete protection, total control, no vomiting, no nausea, score of FLIE) assumed similar values. During the delayed phase, incidence of insomnia (2.9% vs. 0.4%) and heartburn (8.1% vs. 3.6%) was significantly superior in D arm. Conclusions: In breast cancer pts submitted to A+C CT and receiving the same antiemetic prophylaxis for acute emesis, D and AP present similar efficacy and toxicity. Clinical trial information: NCT 00869973.

Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: Analysis of 1,872 patients (pts) in prospective randomized clinical phase III trials (RCTs).

9057 Background: While improvements in the complete control of emesis with NK1s in pts receiving cisplatin (DDP) have been well demonstrated, efficacy reports of this antiemetic class in pts given carboplatin (carbo) or oxaliplatin (oxali) have only been anecdotal. Recent trials documented that emesis with oxali is greater than expected. Guideline groups support using NK1s as part of DDP regimens. Our question relates to the relative magnitude of improvement with aprepitant with newer platinum (PLT) agents in the context of known efficacy with DDP. Methods: We analyzed results of 4 RCTs in 1872 pts receiving chemotherapy. In all trials the control arm on Day 1 was ondansetron (ond) + dexamethasone (dex). The NK1 arms added aprepitant 125 mg on day 1 with 80 mg on days 2 and 3. Control arms for delayed emesis with DDP: dex 8 mg bid in two studies; ond 8 mg bid added in the third; in the aprepitant (investigative) arm only 8 mg of dex daily was given. For delayed emesis with carbo/oxali on the control arm, ...

Aprepitant Vs. Placebo Plus Oral Ondansetron and Dexamethasone for the Prevention of Nausea and Vomiting Associated with Highly Emetogenic Preparative Regimens Prior to Hematopoietic Stem Cell Transplantation: A Prospective, Randomized Double-Blind Phase III Trial.

Abstract 2267Poster Board II-244 Introduction:Both acute and delayed nausea and vomiting are a major problem for patients undergoing highly emetic high dose preparative regimens prior to hematopoietic stem cell transplant (HSCT). Aprepitant (APR) is an NK-1 antagonist FDA approved for the prevention of N/V due to standard dose highly and moderately emetogenic chemotherapy. While several small Phase II studies have suggested its benefit in HSCT, no completed prospective comparisons have been reported. In addition as APR is known to interact with cytochrome P450 isoenzymes involved in the bioactivation of high dose cyclophosphamide, and may interfere with etoposide pharmacokinetics, its impact on regimen related toxicity and long term survival post transplant is unknown. Patients and Methods:We performed a randomized (1:1 randomization) blinded Phase III trial to determine the safety and efficacy of APR for N/V due to ablative preparative regimens. Patients received either placebo (PBO) or oral APR 125mg PO day 1 then 80mg daily during and for 3 days after the preparative regimen was completed, in addition to oral ondansetron 8 mg PO q 8hrs + IV dexamethasone daily during and for 1 day after the preparative regimen. Only PRN lorazepam was permitted for nausea. Due to a known drug interaction between APR and dexamethasone, patients also received blinded dexamethasone doses of 10mg on the placebo arm and 7.5mg on the APR arm. Patients were stratified based on gender, and patients with heavy ETOH use were excluded. Clinical evaluations were performed daily during therapy with the primary endpoint being a CR, defined as: no emesis and no or mild nausea [less than grade (gr) 3 using CTC 2.0 criteria]. Other endpoints included; major response (MR): 1 episode of emesis or moderate nausea; minor response (mR): 2–4 episodes of emesis; and failure (F) : >4 episodes of emesis. Major efficacy (ME) = CR + MR. Other analyses performed included subjective nausea based on a 100 mm visual analog scale (VAS) with 0 = no nausea; amount of PRN antiemetics used to control breakthrough N/V and no emesis all days.. Safety analyses performed included time to engraftment, 30 day survival and progression free survival (PFS) and overall survival (OS). The study began 9/20/04 and completed enrollment 7/18/08. The study was powered (90 pts per arm) to detect a difference of 20 % between the two groups with a significance level of 0.05 using a two-sided t-test. The 181 randomized patients were balanced with respect to age, weight, donor source and h/o N/V with prior chemotherapy. Patients received one of 5 ablative prep regimens: CY/TBI/VP16 (36), CY/TBI (79), IV BU/CY (14), PO BU/CY (34), and BCV(16) Two pts never proceeded to transplant so only 179 pts are eligible for analysis. Ten pts (6 APR/4 PBO) failed to complete the study; data were analyzed as intent to treat. Results:Efficacy: There was a difference in CR rate (primary endpoint) in favor of APR: 81.9% vs 65.8 % for those receiving PBO with 48.9% vs 14.6% respectively meeting this endpoint for the entire study period (p<0.001). In addition, 73.3% of the APR group never experienced a single episode of emesis during the study vs 22.5% of the PBO group (p<0.001). Other response rates were as follows: MR: APR 16% PBO 21.6% (p= 0.011); mR: APR 2.0% PBO 10.3% (p<0.001); F: APR 0.1% PBO 2.2% (p<0.001) ME: APR 97.9% PBO 87.4% (p<0.001). Ave VAS was 16.5 % for the APR group vs 16.9% for the PBO group (0.892). Heartburn was more common in the APR arm (12/90) vs. PBO (6/89) Safety: Days to engraftment for the PBO vs APR groups: ANC: 11.7 vs 11.5d (p = NS), PLT: 14.1 vs 16.4d (p = NS); 30 day survivals were the same for the two groups. The PFS was 28.3 vs 28.6 months for the APR and PBO groups (p=0.8206) and overall survival was identical in the two groups as well (p = 0.5446). Conclusions:When used daily up to 10 days with ablative preparative regimens, aprepitant significantly improved control of acute and delayed regimen-related N/V with a major impact on emesis rates. It appears safe for this indication with no impact on WBC and PLT engraftment as well as PFS and OS. Disclosures:Stiff:Merck: Research Funding. Off Label Use: Aprepitant in BMT setting.

Effect of oral aprepitant in management of delayed chemotherapy-induced nausea and vomiting (DCINV) after high-dose chemotherapy (HDC) and hematopoietic stem cell transplant (HCT)

e20548 Background: This study assessed the safety and efficacy of Aprepitant, a neurokinin 1 receptor antagonist, in the management of DCINV associated with HCT. Methods: Pilot phase I-II RCT, adult patients undergoing ablative HCT. Eligibility Criteria: Presence of DCINV (&gt;1 episode of vomiting/24 hrs or &gt;25 mm on nausea visual analogue scale (VAS) on day 2–14 post- HCT). Control arm: ondansetron + metoclopramide. Aprepitant arm: Same regimen + aprepitant 125 mg on d1 and 80 mg d2–3. Controls with DCINV persisting &gt;72 hours were crossed to treatment arm. Safety endpoints: Primary: myeloid engraftment (ANC&gt;500/μL by d15.) Secondary: platelet engraftment (plts &gt;20,000/μL by d21.) Efficacy endpoints: Primary: no episodes of emesis. Secondary: VAS reduction ≥ 25 mm Results: 12 pts, ages 23–62 yrs, were randomized, 9 to treatment arm. Two of 3 controls crossed over. The study was interrupted prior to completion of accrual to control arm. Results are summarized as median ± SD in the table below. Treatment arm showed no delay in granulocyte and platelet engraftment, less emesis, and little difference in VAS compared to control. No patients in either group developed unexpected grade III-IV toxicities, including VOD or IPS. Conclusions: The use of aprepitant for control of DCINV after myeloablative HCT decreased the frequency of DCINV and had no adverse effect on granulocyte and platelet engraftment. This pilot study supports the safety and efficacy of aprepitant for DCINV in the setting of HCT. [Table: see text] [Table: see text]

Quality of life (QOL) for breast cancer patients receiving aprepitant versus placebo for prevention of chemotherapy induced nausea and vomiting

20549 Background: A Phase III randomized, double-blind placebo controlled trial was done to determine if there is a favourable QOL outcome for patients receiving aprepitant for the prevention of chemotherapy-induced nausea and vomiting (adriamycin 60 mg/m2 + cyclophosphamide 600 mg/m2). Methods: 80 breast cancer patients were entered with 40 in the study treatment arm (aprepitant 125mg; ondansetron 8mg x 2 doses; dexamethasone 20mg on day 1 and aprepitant 80mg QD day 2–3) and 40 patients in the control arm (ondansetron 8mg x 2 doses; dexamethasone 12mg on day 1, and ondansetron 8mg every 12 hours on days 2–3). The QLQ-C30 and FLIE were completed prior to chemotherapy and at the end of day 5. A change score from baseline to day 5 was used in the analysis. Results: The average nausea scores captured by 100 mm visual analog scale between placebo and aprepitant arms were not significant (16.5 vs. 12.8, p=0.554). However, in cycle 1 the QLQ-C30 NV subscale (40.3 vs 20.4, p=0.0066) and appetite loss (57.4 vs 33.3, p=0.0023) were significantly different in favour of aprepitant arm. There were no significant difference with respect to global QOL (-19.9 vs -12.2, p=0.1633). The FLIE nausea subscale (40.1 vs 30.6, p=0.3214) were not significant, but FLIE vomiting subscale (30.4 vs 3.1, p=0.0001) and FLIE overall score (35.3 vs 16.8, p=0.0289) were significant in favour of study treatment. For cycles 2 and 3, we have 36 and 38 patients in the control and study treatment arms respectively. Similar results were found in the FLIE subscales and overall score. Conclusions: There is a significant benefit for the study treatment with respect to QLQ-C30 QOL NV subscale, which is a combined measure on nausea and vomiting. FLIE overall score is an aggregate measurement of 18 items and reflects a significant benefit in favour of aprepitant arm. The majority of treatment effect was due to FLIE vomiting subscale but not FLIE nausea subscale reflecting that aprepitant may provide better control to vomiting than nausea. Study supported by Merck Sharp & Dohme (Asia) Ltd. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Sharp & Dohme (Asia) Ltd.