Evaluation of Efficacy of Adding Aprepitant to Palonosetron and Dexamethasone in Carboplatin and Etoposide Therapy.

Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.

Efficacy and safety of netupitant/palonosetron in preventing nausea and vomiting in diffuse large B cell lymphoma patients undergoing R-CHOP chemotherapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab(R-CHOP) is one of the standard regimens. Given that R-CHOP is highly emetogenic, chemotherapy-induced nausea and vomiting (CINV) prevention is clinically important. However, there is a paucity of studies focusing on these patients. This study aimed to ascertain the effectiveness of an oral fixed-dose combination of netupitant and palonosetron (NEPA) in preventing CINV in patients with DLBCL undergoing first-line R-CHOP chemotherapy. Seventy patients were enrolled in this single-center prospective non-comparative study conducted between November 2020 and May 2023 in South Korea. NEPA was administered 1 h prior to chemotherapy initiation on day 1. The primary endpoint of the study was the complete response rate (no emesis, and no rescue medication) during the acute, delayed, and overall phases, which were assessed over a period of 120 h post-chemotherapy. The complete response rates for NEPA were 90.0% [95% CI 80.5, 95.9] for the acute phase, 85.7% [95% CI 75.3, 92.9] for the delayed phase, and 84.3% [95% CI 73.6, 91.9] for the overall phase, with no-emesis rates (acute: 97.1% [95% CI 97.1, 99.7], delayed: 95.7% [95% CI 88.0, 99.1], overall: 92.9% [95% CI 84.1, 97.6]). NEPA was well tolerated with no severe treatment-emergent adverse events. NEPA exhibited substantial efficacy in mitigating CINV in DLBCL patients undergoing R-CHOP chemotherapy, demonstrating high CR and no-emesis rates, and favorable safety profiles.

Palonosetron in pediatric patients: A single-center, retrospective evaluation of policy and clinical practice guideline discordance.

INTRODUCTION: Clinical practice guidelines (CPGs) recommending palonosetron for the prevention and management of chemotherapy-induced nausea and vomiting (CINV) were adapted for use at our institution. Palonosetron was restricted for use in patients experiencing breakthrough CINV and receiving highly emetogenic chemotherapy (HEC) or undergoing stem cell transplant conditioning and in patients with refractory CINV receiving HEC. Given the significant cost of palonosetron, we aimed to determine the proportion of chemotherapy blocks where palonosetron use was discordant with the institutional policy or source CPG. METHODS: A retrospective review of the health records of patients who received palonosetron between 1 July 2019 and 30 June 2020 was undertaken. Details of palonosetron use, antiemetic regimen and the date and time of each vomit during the acute and delayed phases were collected for each chemotherapy block where palonosetron was given. Discordance with the institutional policy and the source CPG was determined by assessing the indication for palonosetron and the dose. In the subset of chemotherapy blocks where information regarding vomiting episodes was available, the extent of acute phase chemotherapy-induced vomiting (CIV) control was reported. RESULTS: Four hundred thirty-eight chemotherapy blocks, representing 122 patients (mean age 9 years), receiving 595 palonosetron doses were included. Palonosetron use was discordant with institutional policy during most (72%; 314/438) of the chemotherapy blocks analyzed. However, palonosetron use was concordant with the source CPG during most chemotherapy blocks (74%; 326/438). Complete CIV control during the acute phase was observed in 66% (195/295) of chemotherapy blocks where palonosetron was given, irrespective of concomitant antiemetics administered. CONCLUSION: The majority of palonosetron use at our institution was discordant with institutional policy, but concordant with the source CPG. Our institutional policy has since been updated to be more aligned with the source CPG.

Impact of body weight-based dosing of palonosetron and ondansetron on postoperative nausea and vomiting following laparoscopic sleeve gastrectomy: a randomized, double-blind study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a frequent adverse effect following laparoscopic sleeve gastrectomy. Palonosetron with a standard dosing (75 µg) schedule has been questioned due to its low efficiency in obese patients. This study aimed to investigate the effectiveness and safety of the body weight-based dosing of palonosetron in managing PONV following laparoscopic sleeve gastrectomy. METHODS: A single-center, prospective, double-blinded randomized study was conducted between August 2021 and December 2021. Patients who underwent laparoscopic sleeve gastrectomy were prospectively recruited in the study. One hundred patients were randomly divided into palonosetron (Group P) and ondansetron (Group O). The demographic and clinical variables were recorded. The primary outcome of the study was the incidence of PONV between the two groups during the hospitalization. The secondary outcomes were the number of rescue anti-emetic and analgesic medications and the Functional Living Index-Emesis scores. RESULTS: There were 50 patients in each group (Group P and Group O). There were significant differences in the scores of POVN, nausea, and vomiting favoring Group P. In Group P, the rate of patients using rescue anti-emetics was significantly lower. The incidence of complete response and proportion of patients with higher Functional Living Index-Emesis scores were significantly higher in patients using palonosetron. CONCLUSIONS: The use of palonosetron significantly reduced the incidence of PONV following laparoscopic sleeve gastrectomy. There was a significant improvement in the scores of Functional Living Index-Emesis in patients using palonosetron.

A phase II trial of netupitant/palonosetron for prevention of chemotherapy-induced nausea/vomiting in patients receiving BEAM prior to hematopoietic cell transplantation.

Objective: The purpose of this study was to investigate the efficacy and safety of netupitant/palonosetron (NEPA) for the prevention of chemotherapy-induced nausea and vomiting (CINV) for hematopoietic cell transplantation (HCT) patients receiving BEAM therapy. Study Design: This phase II, prospective, intention-to-treat, single-center, single-arm study involved 43 adult patients who received NEPA and dexamethasone for the prevention of CINV due to BEAM conditioning chemotherapy. An interim analysis, performed after 13 patients, determined utility versus futility, and supported continuation to full enrollment. Descriptive statistics were used to report complete response (CR), complete protection, incidence of emesis, and administration of rescue agents. A Kaplan-Meier curve depicted time to first emesis and first rescue medication. Patients self-reported levels of daily nausea descriptively via a CINV Questionnaire. Results: By study end, 13 of 43 patients achieved a CR with an average of 10.6 emesis-free days (SD 0.95) over the 11-day observation period, with no emetic events in any patient during the acute/chemotherapy phase. Nausea was well-controlled throughout the acute therapy phase (Day 1-6) and increased during the delayed phase (Day 7-11) with a peak mean level of 2.79/10 at Day 10. Aside from lower grade (≤2), headaches, constipation, and diarrhea were the most widely reported adverse effects. Conclusion: The combination of NEPA and dexamethasone is safe and effective for the prevention of CINV in patients receiving BEAM conditioning therapy prior to HCT. The regimen demonstrated greater effectiveness in the acute phase versus the delayed phase, with low levels of nausea throughout the study period and complete emesis prevention during chemotherapy.

A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I.

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

Evaluation of palonosetron, fosaprepitant, and olanzapine as antiemetic prophylaxis for fludarabine and melphalan-based conditioning regimens prior to allogeneic hematopoietic stem cell transplants.

BACKGROUND: Limited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu-Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown. OBJECTIVE: The purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu-Mel compared to a historical control group. STUDY DESIGN: This was a retrospective, single-center, cohort review of 123 patients who received a Flu-Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic. RESULTS: The median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31-3.60] vs 3.31 doses [1.61-4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3-122.7] vs 26.2 h [14.7-48.1]; p = 0.016). CONCLUSION: The combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu-Mel-based preparative regimen.

Comparison of palonosetron and ondansetron in preventing postoperative nausea and vomiting in renal transplantation recipients: a randomized clinical trial

Abstract Background: End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal transplantation for a successful outcome in term of an uneventful postoperative period. The study was done to compare the efficacy of palonosetron and ondansetron in preventing early and late-onset PONV in live donor renal transplantation recipients (LDRT). Methods: The prospective randomized double-blinded study was done on 112 consecutive patients planned for live donor renal transplantation. Patients of both sexes in the age group of 18-60 years were randomly divided into two groups: Group O (Ondansetron) and Group P (Palonosetron) with 56 patients in each group by computer-generated randomization. The study drug was administered intravenously (IV) slowly over 30 seconds, one hour before extubation. Postoperatively, the patients were accessed for PONV at 6, 24, and 72 hours using the Visual Analogue Scale (VAS) nausea score and PONV intensity scale. Results: The incidence of PONV in the study was found to be 30.35%. There was significant difference in incidence of PONV between Group P and Group O at 6 hours (12.5% vs. 32.1%, p = 0.013) and 72 hours (1.8% vs. 33.9%, p < 0.001), but insignificant difference at 24 hours (1.8% vs. 10.7%, p = 0.113). VAS-nausea score was significantly lower in Group P as compared to Group O at a time point of 24 hours (45.54 ± 12.64 vs. 51.96 ± 14.70, p = 0.015) and 72 hours (39.11 ± 10.32 vs. 45.7 ± 15.12, p = 0.015). Conclusion: Palonosetron is clinically superior to ondansetron in preventing early and delayed onset postoperative nausea and vomiting in live-related renal transplant recipients.

Comparison of netupitant/palonosetron with 5-hydroxytryptamine-3 receptor antagonist in preventing of chemotherapy-induced nausea and vomiting in patients undergoing hematopoietic stem cell transplantation.

Background: The use of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA) has long been considered the standard regimen for preventing chemotherapy-induced nausea and vomiting (CINV) prior to hematopoietic stem cell transplantation (HSCT). However, their therapeutic outcomes have been unsatisfactory. NEPA, an oral formulation combining the neurokinin-1 receptor antagonist netupitant and the 5HT3RA palonosetron, has received regulatory approval for the management of highly and moderately emetogenic chemotherapy. This study aims to compare the efficacy of NEPA with that of 5HT3RA alone in preventing CINV among patients undergoing multiday conditioning chemotherapy prior to HSCT. Patients and methods: We conducted a retrospective analysis of patients who underwent HSCT between September 2019 and September 2022. Efficacy outcomes were assessed based on the rates of patients achieving complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting, and no significant nausea. Results: The NEPA group consisted of 106 patients, while the 5HT3RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT3RA group during the overall phase (71.7% vs. 32.7%, P<0.001), acute phase (78.3% vs. 43.0%, P<0.001), and delayed phase (84.9% vs. 58.9%, P<0.001). Similarly, rates of CC, no vomiting, and no significant nausea were significantly better in the NEPA group across all phases (P<0.001). Conclusion: NEPA demonstrated superior efficacy compared to 5HT3RA in preventing CINV during all phases of multiday conditioning regimens among patients undergoing HSCT.

Analysis of the Efficacy and Safety of Palonosetron Hydrochloride in Preventing Nausea And Vomiting After TACE: A Retrospective Analysis.

PURPOSE: To investigate the mechanism of nausea and vomiting after TACE, and analyze the efficacy and safety of palonosetron hydrochloride in the prevention of nausea and vomiting after TACE. METHODS: The data of 221 patients who underwent TACE in the Department of Intervention Therapy from August 2018 to August 2020 were collected. The patients were divided into two groups: those who did not use palonosetron hydrochloride before TACE (TACE group, N=116); and those who used palonosetron hydrochloride before TACE (TACE+palonosetron group, N=105). Primary study endpoint: The control rate of nausea and vomiting in the two groups at 0-24 h (acute), 24-120 h (delayed), and 0-120 h. Secondary Study Endpoints: Adverse events of palonosetron hydrochloride. RESULTS: TACE group vs TACE+palonosetron group: 0-24h, 74 vs 44 patients with nausea (63.8% vs 41.9%); 24-120 h, 50 vs 16 patients with nausea (43.1% vs 15.2%); 0-120 h after TACE, 81 vs 50 patients with nausea (69.8% vs 47.6%). 0-24h, 52 vs 26 patients with vomiting (44.8% vs 24.8%); 24-120 h, 24 vs 8 patients with vomiting (20.7% vs 7.6%); 0-120 h after TACE, 64 vs 26 patients with vomiting (55.2% vs 24.8%). The incidence of nausea and vomiting after TACE was significantly lower in the TACE+palonosetron group than in the TACE group (p < 0.05). CONCLUSION: Palonosetron hydrochloride can significantly reduce the incidence of nausea and vomiting in patients after TACE, with exact effect and high safety.

Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.

A suspected case of serotonin syndrome induced by palonosetron and ramosetron administration.

Serotonin syndrome occurs when serotonin (5-hydroxytryptamine, 5-HT) levels increase and is accompanied by symptoms of mental status changes, neuromuscular abnormalities, and autonomic hyperactivity. Serotonin receptor 3 antagonists, such as palonosetron or ramosetron, are commonly used for their antiemetic effects during general anesthesia. However, overdosage of these drugs carries a risk of serotonergic toxicity as they increase serum serotonin levels due to inhibition of serotonin reuptake. Serotonin syndrome caused by 5-HT3 antagonists is thought to be caused by the synergistic effects of high doses of serotonergic drugs or the combination of two or more serotonergic drugs with different mechanisms of action. The incidence of serotonin syndrome is unknown because it is a rare condition that cannot be selected for in randomized clinical trials. Therefore, physicians must focus on the clinical manifestations of the syndrome and manage patients before the condition becomes life-threatening.

Single-dose NEPA versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy.

INTRODUCTION: Non-inferiority of NEPA (fixed combination of NK1 receptor antagonist (RA), netupitant, and 5-HT3 RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention. METHODS: This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase. RESULTS: The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012). CONCLUSION: A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.

Assessment of the change of antiemetic prophylaxis from double to triple combination in patients with high dose carboplatin chemotherapy.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy. METHODS: Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ2 test. RESULTS: Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p = 0.0115) and delayed phase (97.6% vs 90.7%, p = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p = 0.70). CONCLUSIONS: TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.

Effectiveness of Palonosetron, 1-Day Dexamethasone, and Aprepitant in Patients Undergoing Carboplatin-Based Chemotherapy.

INTRODUCTION: Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy. METHODS: Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR. RESULTS: No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period. CONCLUSION: Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.

Dexamethasone-sparing regimens with NEPA (netupitant/palonosetron) for the prevention of chemotherapy-induced nausea and vomiting in older patients (>65 years) fit for cisplatin: A sub-analysis from a phase 3 study.

INTRODUCTION: We recently demonstrated the non-inferiority of two dexamethasone (DEX)-sparing regimens with an oral fixed-combination of netupitant and palonosetron (NEPA) versus the guideline-recommended DEX use for cisplatin-induced nausea and vomiting. Since prevention of chemotherapy-induced nausea and vomiting is critical in older patients, we retrospectively evaluated the efficacy of the DEX-sparing regimens in this subset. MATERIALS AND METHODS: Chemo-naive patients aged >65 years treated with high-dose cisplatin (≥70 mg/m2) were eligible. Patients received NEPA and DEX on day 1 and were randomized to receive either (1) no further DEX (DEX1), (2) oral low-dose DEX (4 mg) on days 2-3 (DEX3), or (3) the guideline-recommended standard DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint of the parent study was complete response (CR; no vomiting and no use of rescue medication) during the overall phase (days 1-5). No significant nausea (NSN; none or mild nausea) and the proportion of patients reporting no impact on daily life (NIDL) which was evaluated by the Functional Living Index-Emesis questionnaire on day 6 (overall combined score > 108), were secondary endpoints. RESULTS: Among the 228 patients in the parent study, 107 were > 65 years. Similar CR rates [95% confidence intervals (CI)] were observed in patients over 65 years across treatment groups [DEX1: 75% (59.7-86.8%); DEX3: 80.6% (62.5-92.6%); DEX4: 75% (56.6-88.5%)] as well as versus the total study population. NSN rates were also similar in the older-patients across treatment groups (p = 0.480) but were higher compared with the total population. Similar rates of NIDL (95% CI) were reported in the older-patient subset across treatment groups [DEX1: 61.5% (44.6-76.6%); DEX3: 64.3% (44.1-81.4%); DEX4: 62.1% (42.3-79.3%); p = 1.0] during the overall phase, as well as versus total population. A similar proportion of older patients across treatment groups experienced DEX-related side effects. DISCUSSION: This analysis shows that older-patients who are fit for cisplatin benefit from a simplified regimen of NEPA plus single-dose DEX with neither loss in antiemetic efficacy nor the adverse impact on patient daily functioning. The study was registered on ClinicalTrials.gov (identifier NCT04201769) on 17/12/2019 (retrospectively registered).

Real-World Treatment Outcomes, Healthcare Resource Use, and Costs Associated with Antiemetics Among Cancer Patients on Cisplatin-Based Chemotherapy.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment outcomes, resource utilization, and costs associated with antiemetic use to prevent CINV in a broad US population who received cisplatin-based chemotherapy. METHODS: Data from the STATinMED RWD Insights Database was collected from January 1, 2015 to December 31, 2020. Cohorts included any patients that had at least one claim for fosnetupitant + palonosetron (NEPA) or fosaprepitant + palonosetron (APPA) and evidence of initiating cisplatin-based chemotherapy. Logistic regression was used to evaluate nausea and vomiting visits within 14 days after chemotherapy, and generalized linear models were used to examine all-cause and CINV-related healthcare resource utilization (HCRU) and costs. RESULTS: NEPA was associated with significantly lower rates of nausea and vomiting visits after chemotherapy (p = 0.0001), including 86% greater odds of nausea and vomiting events for APPA during the second week after chemotherapy (odds ratio [OR] = 1.86; p = 0.0003). The mean numbers of all-cause inpatient visits (p = 0.0195) and CINV-related inpatient and outpatient visits were lower among NEPA patients (p < 0.0001). These differences corresponded to 57% of NEPA patients and 67% of APPA patients having one or more inpatient visits (p = 0.0002). All-cause outpatient costs and CINV-related inpatient costs were also significantly lower for NEPA (p < 0.0001). The mean number of all-cause outpatient visits, all-cause inpatient costs, and CINV-related outpatient costs was not significantly different between groups (p > 0.05). CONCLUSION: In this retrospective study based on claims data, NEPA was associated with lower rates of nausea and vomiting and lower CINV-related HCRU and costs compared to APPA following cisplatin-based chemotherapy. These results complement clinical trial data and published economic models supporting the use of NEPA as a safe, effective, and cost-saving antiemetic for patients undergoing chemotherapy.

Palonosetron as prophylaxis for post-discharge nausea and vomiting: a prospective, randomised, double-blind, placebo-controlled trial in ambulatory surgery.

BACKGROUND: Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting anti-emetic, decreases the incidence of PDNV in high-risk patients. METHODS: In this prospective, randomised, double-blind, placebo-controlled trial, 170 male and female patients undergoing ambulatory surgery under general anaesthesia, with a high predicted risk for PDNV, were randomised to receive either palonosetron 75 µg i.v. (n=84) or normal saline (n=86) before discharge. During the first 3 postoperative days (PODs), we measured outcomes using a patient questionnaire. The primary outcome was the incidence of a complete response (no nausea, vomiting, or use of rescue medication) until POD 2. Secondary outcomes included the incidence of PDNV each day until POD 3. RESULTS: The incidence of a complete response until POD 2 was 48% (n=32) in the palonosetron group and 36% (n=25) in the placebo group (odds ratio 1.69 [95% confidence interval: 0.85-3.37]; P=0.131). No significant difference in the incidence of PDNV was observed between the two groups on the day of surgery (47% vs 56%; P=0.31). Significant differences in the incidence of PDNV were found on POD 1 (18% vs 34%; P=0.033) and POD 2 (9% vs 27%; P=0.007). No differences were observed on POD 3 (15% vs 13%; P=0.700). CONCLUSIONS: Compared with placebo, palonosetron did not reduce the overall incidence of post-discharge nausea and vomiting up to postoperative day 2. The lower incidence of post-discharge nausea and vomiting on poatoperative days 1 and 2 in the palonosetron group requires further investigation. CLINICAL TRIAL REGISTRATION: EudraCT 2015-003956-32.

A comparison of prophylactic antiemetic therapy with palonosetron and dexamethasone as single-agents or in combination in adult patients undergoing laparoscopic surgery: A randomized trial.

Background: The incidence of postoperative nausea and vomiting (PONV) is quite high after laparoscopic surgeries. This study endeavors to compare the efficacy of the combination of palonosetron and dexamethasone with that of either drug alone in the prevention of PONV in patients undergoing laparoscopic surgeries. Methods: This randomized, parallel-group trial was done on ninety adults of American Society of Anesthesiologists Grade I and II patients aged 18-60 years undergoing laparoscopic surgeries under general anesthesia. The patients were randomly divided into three groups of thirty patients each. Group P (n = 30) received palonosetron 0.075 mg intravenously (iv), Group D (n = 30) received dexamethasone 8 mg iv and Group P + D (n = 30) received palonosetron 0.075 mg and dexamethasone 8 mg iv. The primary outcome was incidence of PONV in 24 h, and the secondary outcome was a number of rescue antiemetics required. To compare the proportions in the groups, unpaired t-test, Mann-Whitney U-test, Chi-square test, or Fisher's exact test was applied. Results: We found that the overall incidence of PONV was 46.7% in Group P, 50% in Group D, and 43.3% in Group P + D during the first 24 h. Rescue antiemetic was required in 27% of the patients in Group P and Group D compared to 23% of the patients in Group P + D and twice in 3% of the patients in Group P, 7% of the patients in Group D, and none in Group P + D which were not significant. Conclusions: The combination therapy of palonosetron plus dexamethasone did not significantly reduce the incidence of PONV when compared with either drug alone.

Fosnetupitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Short Review and Clinical Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel neurokinin-1 (NK1) receptor antagonist fosnetupitant, a phosphorylated prodrug formulation of netupitant, was approved in Japan in 2022. Fosnetupitant is one of the standard treatments for the prevention of CINV in patients who are receiving highly (any treatment where CINV occurs in more than 90% of patients) or moderately (where CINV occurs in 30-90% of patients) emetogenic chemotherapies. The aim of this commentary is to describe the mechanism of action, tolerability, and antiemetic efficacy of single-agent fosnetupitant in the prevention of CINV, and to discuss its clinical application, in order to aid optimal use.