Our previous study showed that the preventive effects of fosnetupitant (F-NTP) against chemotherapy-induced nausea and vomiting (CINV) were superior to those of fosaprepitant (F-APR) or aprepitant (APR). To evaluate the cost-effectiveness of F-NTP compared with F-APR or APR in Japan, a cost-utility analysis was performed. A decision tree model was developed based on real-world data to compare the CINV prevention ability of each neurokinin-1 receptor antagonist (NK1 RA) in Japanese patients receiving cisplatin-based regimens. We evaluated the patients 7days after the first course of treatment. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated to examine the cost-effectiveness of the antiemetic therapy. The probabilities of health states and medical costs were derived from the results of our previous study. These cost-utility analyses were performed from the perspective of the payers. The incremental QALYs of F-NTP relative to F-APR and APR were 0.00180 and 0.00153, respectively. The ICER of F-NTP relative to F-APR was 22,802.21 US dollars (USD) per QALY gained, which was lower than the willingness-to-pay (WTP) threshold (38,043.06 USD: 5 million Japanese Yen/QALY). Contrastingly, the ICER of F-NTP relative to APR was 40,119.64 USD/QALY, which was slightly above the WTP threshold, indicating that F-NTP may be slightly less cost-effective. F-NTP is more cost-effective than F-APR, but slightly less cost-effective than APR.

Fosaprepitant improves cyclophosphamide-induced bladder damage by alleviating inflammatory response in mice

The frequency rate of injection site reactions (ISR) due to fosaprepitant meglumine (Fos APR) has been shown to vary depending on the types of combined anticancer drug. This study aimed to elucidate the impact of Fos APR on ISR in patients receiving paclitaxel and carboplatin, with and without bevacizumab therapy (TC±Bev). This study focused on patients with gynecologic cancer (n=93) who received TC±Bev administration at Fujita Health University Hospital from March 2016 to February 2020, and monitored up to six cycles. The patients were randomly assigned to the Fos APR group (n=47) and the Aprepitant (APR) group (n=46). Using Visual Infusion Phlebitis (VIP) scores, ISR was evaluated by comparing the VIP scores of all cycles using a linear mixed model. The risk factors that contribute to the occurrence of vascular pain throughout all cycles were also examined. The VIP scores of all cycles showed a near significant intergroup difference (p=0.071). Factors that affected the development of vascular pain included Fos APR and age (p=0.027 and 0.049, respectively). Regarding age, patients aged <65 years had a higher risk. Four patients underwent a switch from the originally assigned neurokinin-1 receptor antagonist; in all of these cases, Fos APR was changed to APR for vascular pain. Fos APR may increase the risk for ISR associated with TC±Bev therapy for gynecological cancer.

ObjectiveThe purpose of this study was to evaluate the cost-effectiveness and budget impact of fosaprepitant (FosAPR)-containing regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) from the Chinese payer's perspective.MethodsA decision tree model was established to measure the 5-day costs and health outcomes between the APR-containing regimen (aprepitant, granisetron, and dexamethasone) and FosAPR-containing regimen (fosaprepitant, granisetron, and dexamethasone). Clinical data were derived from a randomized, double-blind controlled trial on Chinese inpatients who received HEC. Quality-adjusted life-years (QALYs) were used to estimate the utility outcomes and the incremental cost-effectiveness ratio (ICER) was calculated to assess the economics of FosAPR. A static budget impact model was developed to assess the impact of FosAPR as a new addition to the National Reimbursement Drug List (NRDL) on the medical insurance fund within 3 years in Nanjing, China.ResultsCompared with APR, FosAPR had a mean health-care savings of ¥121.56 but got a reduction of 0.0001815 QALY, resulting in an ICER of ¥669926.19 per QALY. Deterministic sensitivity analysis revealed that the cost of APR was the most influential factor to the ICER. The cost of FosAPR and the complete control rate of the delayed period also had a high impact on the results. According to the probabilistic analysis, the acceptability of FosAPR was more than 80% when the Chinese willingness-to-pay (WTP) was ¥215,999. FosAPR would lead to a 3-year medical insurance payment increase of ¥1.84 million compared with ¥1.49 million before FosAPR entered NRDL in Nanjing. The total budget increased with a cumulative cost of ¥694,829 and covered an additional 341 patients who benefited from FosAPR in Nanjing. Deterministic sensitivity analysis showed that the model of budget impact analysis was stable.ConclusionFosAPR had a similar treatment effect to APR but was cost-effective in China at the current WTP threshold. The total budget of medical insurance payments of Nanjing slightly increased year by year after the inclusion of FosAPR. Its inclusion in the NRDL would be acceptable and also expand the coverage of patients who benefited from FosAPR.

BACKGROUNDFosnetupitant (FosNTP), an intravenous neurokinin 1 receptor antagonist, demonstrated a favorable safety profile with a potentially low risk of injection site reactions (ISRs) and promising antiemetic efficacy in patients receiving cisplatin‐based highly emetogenic chemotherapy in a previous phase 2 study. We conducted a randomized, double‐blind safety study to evaluate the safety profile of FosNTP, including ISRs, in patients receiving doxorubicin‐cyclophosphamide or epirubicin‐cyclophosphamide (AC/EC) chemotherapy.METHODSPatients scheduled to receive AC/EC were randomized 1:1 to receive 235 mg of FosNTP or 150 mg of fosaprepitant (FosAPR), both in combination with 0.75 mg of intravenous palonosetron and 9.9 mg of dexamethasone on day 1. The stratification factors were age category (<55 vs ≥55 years) and study site. The primary end point was the incidence of treatment‐related adverse events (TRAEs) with FosNTP.RESULTSOverall, 102 patients were randomized to FosNTP (n = 52) or FosAPR (n = 50), and all were treated with the study drug and evaluated for safety. The primary end point, the incidence of TRAEs, was similar with FosNTP (21.2%; 95% confidence interval [CI], 11.1%‐34.7%) and FosAPR (22.0%; 95% CI, 11.5%‐36.0%), with any‐cause ISRs observed in 5.8% and 26.0% of patients, respectively, and treatment‐related ISRs observed in 0% and 10.0%, respectively. The overall (0‐120 hour) complete response (defined as no emetic event and no rescue medication) rate, standardized by age category in the full analysis set, was 45.9% (23 of 51 patients) with FosNTP and 51.3% (25 of 49 patients) with FosAPR.CONCLUSIONSFosNTP demonstrated a favorable safety profile with a very low risk of ISRs in the AC/EC setting.

12099 Background: Fosnetupitant (FN) is a phosphorylated pro-drug of netupitant that has high binding affinity for the neurokinin-1 (NK-1) receptor and a long half-life of 70 h. This phase 3 study is the first head-to-head study to compare two NK-1 receptor antagonists, FN and fosaprepitant (FA), in combination with palonosetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (JapicCTI-194611). Methods: Patients scheduled to receive cisplatin (≥70 mg/m2) -based chemotherapy were randomly assigned 1:1 to receive FN 235 mg or FA 150 mg, in combination with palonosetron 0.75 mg and dexamethasone (9.9 mg on day 1, 6.6 mg on days 2-4). The stratification factors were sex, age category (&lt;55 vs. ≥55 years), and site. The primary endpoint was the complete response (CR; no emetic events and no rescue medication) rate, stratified by sex and age category, during the overall phase (0-120 h) to show the non-inferiority (margin, -10%) of FN to FA. The secondary endpoints were: CR rate, complete protection rate, total control rate, no nausea rate, no emetic events rate in each period [i.e., acute (0-24 h), delayed (24-120 h), overall, 0-168 h and 120-168 h], time to treatment failure, and safety, including injection site reactions (ISRs). Assessment of efficacy was continued until 168 h after the initiation of cisplatin. Some eligible patients were evaluated for safety and efficacy of FN for up to four cycles. Results: Between February 2019 and March 2020, total 795 patients were enrolled in the study. The study drug was administered to 785 patients (n=392 in FN vs. n=393 in FA), and all of them were evaluated for efficacy and safety. Baseline characteristics were generally balanced between the two groups. The adjusted overall CR rate was 75.2% in FN vs. 71.0% in FA [MH common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), thus demonstrating non-inferiority of FN to FA. Regarding the other secondary endpoints of efficacy until 168 h, FN was favorable against FA, especially the CR rate during 0-168 h (73.2% in FN vs. 66.9% in FA) (Table). The incidence rates of treatment-related adverse events were 22.2% in FN vs. 25.4% in FA, whereas those of ISRs with any cause or with treatment-related were 11.0% or 0.3% in FN vs 20.6% or 3.6% in FA, respectively ( p&lt;0.001). Conclusions: FN demonstrated non-inferiority to FA, with a favorable safety profile and lower risk for ISRs. For the period beyond 120 h after initiation of chemotherapy, FN may have the potential to improve the prevention of “beyond delayed” CINV. Clinical trial information: JapicCTI-194611. [Table: see text]

12094 Background: Fosnetupitant (FN) is a phosphorylated pro-drug of netupitant that has high binding affinity and selectivity for the neurokinin 1 receptor and a long half-life of 70 h. Recent studies have reported that fosaprepitant (FA) has a risk for developing injection site reactions (ISRs) in patients with breast cancer who receive doxorubicin-cyclophosphamide/epirubicin-cyclophosphamide (AC/EC)-based treatments. Previous studies have shown that FN may have a low risk of ISRs and could potentially address this unmet medical need. The present study (JapicCTI-194691) was intended to evaluate the safety profile, including ISRs, of FN in patients receiving AC/EC treatment. For exploratory purposes, we set the FA group as the exploratory arm. A separate pivotal phase 3 study (JapicCTI-194611) was conducted to verify the efficacy and safety of FN compared with FA in patients receiving cisplatin-based chemotherapy. Methods: Patients scheduled to receive AC/EC were randomly assigned 1:1 to receive FN 235 mg or FA 150 mg in a double-blind manner, in combination with intravenous palonosetron (PALO) 0.75 mg and dexamethasone (DEX) 9.9 mg on day 1. The stratification factors were age class ( &lt; 55 years vs. ≥55 years) and site. The primary endpoint was the incidence of treatment-related adverse events (TRAEs) of FN. In addition, the ISRs were investigated as secondary endpoints. Efficacy outcomes were also evaluated as secondary endpoint. Results: Between April 2019 and March 2020, total 102 patients were enrolled in the study. Fifty-two patients were randomized to the FN group and 50 to the FA group, and all of them were treated with the study drug and evaluated for safety. The baseline characteristics were generally balanced, except for the history of motion sickness (54.9% vs. 44.9%) and non-smokers (78.4% vs. 63.3%) in the FN and FA groups, respectively, which are considered as risk factors for chemotherapy-induced nausea and vomiting. The primary endpoint, the incidence of TRAEs was 21.2% (n = 11) (95% CI 11.1% – 34.7%) in the FN group, which was similar to that in the FA group [22.0% (n = 11) (95% CI 11.5% - 36.0%) ]. Any cause or treatment-related ISRs were observed in 5.8% (n = 3) and 0% (n = 0), respectively, in the FN group and 26.0% (n = 13) and 10.0% (n = 5), respectively, in the FA group. The overall (0–120 h) complete response (no emetic event and no rescue medication) rate standardized by age category was 45.9% (n = 23) in the FN group and 51.3% (n = 25) in the FA group. Conclusions: The safety of FN in combination with PALO and DEX was favorable. Risk of ISR by FN was quite low in the AC/EC setting. Clinical trial information: JapicCTI-194691.

PDG5 Cost- Effectiveness Analysis between Aprepitant and Fosaprepitant in the Prevention of Chemotherapy-Induced Nausea and Vomiting in China

Comparative Cost-utility Analysis Between Aprepitant- and Fosaprepitant-containing Regimens To Prevent Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Japan

In breast cancer patients on a fluorouracil-epirubicin (EPI)-cyclophosphamide (FEC) regimen and intravenous fosaprepitant (FAP) during chemotherapy, infusion-site adverse events such as vascular pain and induration and/or phlebitis are observed. In the present study, adverse events induced by the FEC regimen and FAP, a prodrug of aprepitant (AP), were studied based on the vascular tissue distribution of EPI in rats. Rats were treated with intravenous FAP (3 mg/kg, 10 min-constant rate infusion) or oral AP (3 mg/kg) and then intravenous EPI (1 mg/kg, 5 min-constant rate infusion) as follows: FAP-S Group, FAP and then EPI was infused from the same site on the jugular vein; FAP-D Group, FAP and then EPI was infused from different jugular veins (left and right); and AP Group, AP was administered orally and EPI was infused from the jugular vein. Concentrations of EPI in vascular tissue at the EPI infusion sites and opposite sites of the jugular vein (left and right, respectively) were measured at 30 min and 24 h after EPI infusion. Histological observation of the EPI infusion site was also made separately. In rats, the tissue concentrations of EPI at the infusion site in the FAP-S group were higher than those in the FAP-D and AP groups. Inflammation and necrosis were observed at the EPI infusion-site vascular tissue of the FAP-S group, but not of the FAP-D and AP groups. These findings could aid the development of an approach to avoid infusion-site adverse events in anthracycline-based chemotherapy in the clinical practice.

Abstract Background: Aprepitant has demonstrated efficacy in patients with breast cancer receiving anthracycline and cyclophosphamide (AC)-based chemotherapy, but the efficacy of single-day fosaprepitant in patients receiving moderately emetogenic chemotherapy (MEC) regimens not including AC has not been widely reported. In a post hoc analysis, we explored prevention of chemotherapy-induced nausea and vomiting (CINV) in a subgroup of patients with breast cancer using a single-day triple-antiemetic fosaprepitant (FA) regimen compared to a standard 3-day control regimen. Methods: This was a global, randomized, double-blind, parallel-group, phase 3 study in adult subjects who were scheduled to receive an intravenous (IV) dose of ≥1 MEC on the first day of treatment (NCT01594749). AC regimens were excluded as they are no longer considered MEC. Subjects were randomly assigned to a control or FA regimen (1:1). The control regimen consisted of oral ondansetron 8 mg, dexamethasone 20 mg, and IV saline as placebo before the first dose of MEC on day 1, and oral ondansetron 8 mg 8 hours after the first dose and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with dexamethasone 12 mg and a single dose of IV FA 150 mg before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. The primary end point was complete response (CR; no vomiting or rescue medication) in the delayed phase (25-120 hours after chemotherapy initiation). Results: Overall, 1000 subjects were included in the intention-to-treat population (FA: N = 502; control: N = 498), and the primary end point was met (P &amp;lt; 0.001; FA vs control). In a subset of 231 subjects with breast cancer, 110 received the FA regimen and 121 the control regimen. Subjects were female, with the exception of 1 male in the FA group, most were aged 50 years or older (67%), and 210 subjects (91%) received single-day MEC regimens on day 1. Among them, 17 subjects in the FA group (8.1%) and 27 in the control group (12.9%) received carboplatin-based chemotherapy, and the remaining 166 subjects received other MEC regimens. CR in the delayed phase was achieved by 76.4% of subjects in the FA group and 68.6% in the control group (difference, 7.8%). Approximately 79% in each group had no vomiting episodes in the overall phase (hours 0-120). Completion on study medication was high, at approximately 98% in each group. Adverse events (AEs) were similar between groups: overall AEs occurred in 79.1% and 73.6% of subjects in the FA and control groups, respectively. AEs considered treatment related by the investigator were also balanced by treatment arm, occurring in 14 (12.7%) and 13 (10.7%) subjects in the FA and control groups, respectively; there was 1 treatment-related serious AE (hypersensitivity) that occurred in the FA group. Conclusions: A single-day IV FA regimen is effective for preventing CINV in breast cancer patients receiving MEC. Citation Format: Weinstein C, Jordan K, Green S, Khanani S, Beckford-Brathwaite E, Vallejos W, Pong A, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer receiving moderately emetogenic chemotherapy regimens [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-11.

e21685 Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing symptom of cancer treatment; in lung cancer, carboplatin is commonly used. In a post hoc analysis, we explored prevention of CINV in lung cancer patients with a single-day triple-antiemetic fosaprepitant (FA) regimen compared with a standard 3-day control regimen. Methods: This was a phase 3, global, randomized, double-blind, parallel-group study in adults scheduled to receive an intravenous (IV) dose of ≥1 moderately emetogenic chemotherapy (MEC) on treatment day 1 (NCT01594749). Subjects were randomly assigned 1:1 to a control or FA regimen. The control regimen consisted of 8 mg oral ondansetron, 20 mg dexamethasone, and IV saline as placebo before the first dose of MEC on day 1, and 8 mg oral ondansetron 8 hours after the first dose and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with 12 mg dexamethasone and a single dose of 150 mg IV FA before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. The primary end point was complete response (CR; no vomiting or rescue medication) in the delayed phase (25-120 hours). Results: Overall, 1000 subjects were included in the intention-to-treat population (FA: n = 502; control: n = 498). The primary end point was met ( P &lt; 0.001; FA vs control). In a subset of 254 subjects with lung cancer (71% male), 129 in FA regimen and 125 in control regimen, most (98%) received carboplatin-based chemotherapy. CR in the delayed phase was achieved by 80.6% in the FA group and 74.4% in the control group (difference, 6.2%). More subjects had no vomiting episodes in the FA (85.3%) vs control (78.4%) groups within the delayed phase (difference, 6.9%), and overall time-to-first vomiting episode was longer for subjects in the FA group. Adverse events (AEs) were similar between groups: overall AEs occurred in 57.7% and 54.8%, and serious AEs occurred in 12.3% and 12.1% in the FA and control groups, respectively. No serious AEs were considered related to study medication. Conclusions: A single-day IV FA regimen is effective for preventing CINV in patients with lung cancer receiving carboplatin. Clinical trial information: NCT01594749.

1435O - Exploration of the heterogeneity of moderately emetogenic chemotherapy on response to fosaprepitant in a randomized phase 3 trial

9502 Background: The purpose of the study was to compare the effectiveness of olanzapine (OLN) and fosaprepitant (FOS) for the prevention of nausea and vomiting in patients receiving concurrent hig...

9629 Background: This is the first study performed to directly evaluate the efficacy and safety of a single dose of intravenous (IV) fosaprepitant (FA), an NK1 receptor antagonist, used with a 5-HT...

Although palonosetron (PALO) and NK1 receptor antagonist both reduce chemotherapy-induced nausea and vomiting, no comparison trial in moderately emetogenic chemotherapy (MEC) had been reported. The purpose of this study was to find out which drug combinations are preferable for patients receiving MEC. Chemotherapy-naive patients receiving MEC were randomized to two groups; group A first received PALO therapy [PALO plus 1-day dexamethasone (DEX)], and group B first received fosaprepitant (FAPR) therapy [FAPR, granisetron (GRAN), and DEX]. Patients were re-allocated to the other therapy, respectively, for the second cycle of chemotherapy. We administered intravenous PALO (0.75 mg) and DEX (9.9 mg) to the PALO therapy group, and FAPR (150 mg), DEX (4.95 mg), and GRAN (3 mg) to the FAPR therapy group, on Day 1. Complete response (CR) was the primary endpoint; complete control (CC), total control (CT), and the therapy chosen by the patients for their third and following cycles of antiemetic therapy were the secondary endpoints. We evaluated CR, CC, and TC in the acute phase, in the delayed phase, and over the whole period. A total of 35 patients and 70 cycles of therapy was evaluable for analysis. No significant difference was found at all evaluation points. Overall CR rates for PALO and FAPR therapy were 74 vs 69 % (P = 0.567), CC rates 66 vs 69 % (P = 0.521), and TC rates 46 vs 60 % (P = 0.235), respectively. Patients also showed no clear preference for their third and following cycles of chemotherapy, choosing both regimens almost equally often (PALO 10 vs FAPR 13). PALO and 1-day DEX is almost equivalent to FAPR, GRAN, and DEX for MEC.

TPS9664 Background: CINV is a common side effect that may occur in acute (0-24 hours [h]) and delayed (25-120 h) post-chemotherapy phases. Aprepitant is a potent and selective oral NK1 receptor ant...

Synthesis of the major isomers of Aprepitant and Fosaprepitant