Netupitant 300mg / Palonosetron hydrochloride 500micrograms capsules

BACKGROUND: Despite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes. METHODS: We conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model. RESULTS: Seven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA's particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60). CONCLUSION: NEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.

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Correction to: Comparative effectiveness of netupitant-palonosetron plus dexamethasone versus aprepitant

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NEPA, a fixed-antiemetic combination of netupitant and palonosetron, is available via two administration routes (oral and intravenous). A new oral suspension was developed to offer a more convenient option for patients. This study evaluated the bioequivalence between the oral capsule and the oral suspension. Open-label, randomized, single-center phase I trial conducted according to a two-treatment, four-period, two-sequence replicative design. Two treatments were investigated for bioequivalence: a 10-mL oral suspension (Test [T]) and the hard capsule (Reference [R]), both containing 300 mg netupitant/0.5 mg palonosetron. Healthy individuals were randomized (1:1) to receive two doses of both Test and Reference formulations, in either T-R-T-R or R-T-R-T sequence. The primary objective was to demonstrate AUC0-t bioequivalence of netupitant and palonosetron after a single dose of Test and Reference formulations. In total, 72 participants were included. The geometric mean plasma concentration–time profiles of netupitant and palonosetron were similar for the Test and Reference formulations. The AUC0-t geometric means of both analytes were similar for the Test and Reference formulations. The 90% confidence interval of the Test/Reference ratios for AUC0-t of netupitant and palonosetron were within the acceptance range for bioequivalence of 80–125%. The AUC0-t variability was moderate for netupitant and low for palonosetron. Both formulations were well tolerated. The NEPA oral suspension is pharmacokinetically bioequivalent to the capsule formulation in healthy individuals, with no new safety concerns. These findings support NEPA oral suspension as a potentially beneficial option for patients who prefer an oral suspension over a hard capsule and for those with swallowing difficulties. EUCT Number: 2023–504355-28–00 (25/08/2023).

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INTRODUCTION: Antineoplastic drugs may induce several side effects, including chemotherapy-induced nausea and vomiting (CINV). Two neurotransmitters play a central role in mediating the emetic response: serotonin acting on the 5HT3 receptor and the substance P targeting the NK1 receptor. Indeed, a combination of a 5HT3 receptor antagonist (5HT3-RA) and a NK1 receptor antagonist (NK1-RA) together with dexamethasone has been shown to be very effective. In fact, this combination is actually widely used and recommended for CINV prophylaxis for highly emetogenic cisplatin-based adriamycin/cyclophosphamide (AC) and carboplatin-based regimens. NEPA (netupitant/palonosetron) is the only fixed combination antiemetic available and it is composed by the long-lasting second-generation 5HT3-RA palonosetron and the highly selective NK1-RA netupitant. AIM: The aims of this short review were to analyze the role of NEPA in CINV prophylaxis and management taking in account the risk factors related to the patient and to the antineoplastic treatment. EVIDENCE REVIEW: CINV development is not only correlated to the emetogenic potential of the antineoplastic drugs but is also very influenced by the patient characteristics and history, such as gender, age, alcohol intake, nausea during pregnancy and motion sickness. In pivotal and post-registration studies, NEPA has demonstrated to be effective and safe in both highly and moderately emetogenic chemotherapy. CONCLUSION: A proper assessment of both chemotherapy- and patient-related risk factors is paramount to properly evaluate an appropriate prophylaxis of CINV and NEPA by simplifying the therapy, guarantees fully adherence to antiemetic guidelines, and consequently improves the control of CINV, especially in high risk patients.

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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: ) 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).

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INTRODUCTION: This post-hoc analysis retrospectively assessed data from two recent studies of antiemetic regimens for chemotherapy-induced nausea and vomiting (CINV). The primary objective was to compare olanzapine-based versus netupitant/palonosetron (NEPA)-based regimens in terms of controlling CINV during cycle 1 of doxorubicin/cyclophosphamide (AC) chemotherapy; secondary objectives were to assess quality of life (QOL) and emesis outcomes over four cycles of AC. METHODS: This study included 120 Chinese patients with early-stage breast cancer who were receiving AC; 60 patients received the olanzapine-based antiemetic regimen, whereas 60 patients received the NEPA-based antiemetic regimen. The olanzapine-based regimen comprised aprepitant, ondansetron, dexamethasone, and olanzapine; the NEPA-based regimen comprised NEPA and dexamethasone. Patient outcomes were compared in terms of emesis control and QOL. RESULTS: During cycle 1 of AC, the olanzapine group exhibited a higher rate of 'no use of rescue therapy' in the acute phase (olanzapine vs NEPA: 96.7% vs 85.0%, P=0.0225). No parameters differed between groups in the delayed phase. The olanzapine group had significantly higher rates of 'no use of rescue therapy' (91.7% vs 76.7%, P=0.0244) and 'no significant nausea' (91.7% vs 78.3%, P=0.0408) in the overall phase. There were no differences in QOL between groups. Multiple cycle assessment revealed that the NEPA group had higher rates of total control in the acute phase (cycles 2 and 4) and the overall phase (cycles 3 and 4). CONCLUSION: These results do not conclusively support the superiority of either regimen for patients with breast cancer who are receiving AC.

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Background The use of 5-hydroxytryptamine-3 receptor antagonists (5HT 3 RA) 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 5HT 3 RA 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 5HT 3 RA 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 5HT 3 RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT 3 RA 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 5HT 3 RA in preventing CINV during all phases of multiday conditioning regimens among patients undergoing HSCT.

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Abstract Purpose Netupitant 300 mg/palonosetron 0.5 mg (NEPA) would be ideal as antiemetic prophylaxis for patients receiving weekly cisplatin, as it would reduce concurrent medication intake compared to the 3-day aprepitant regimen. However, due to the longer half-life of netupitant (~ 88 h), weekly administration could potentially lead to accumulation and toxicity. This study aims to investigate the safety and antiemetic efficacy of weekly administration of NEPA plus dexamethasone (DEX) in patients treated for cervical cancer with radiotherapy and weekly cisplatin 40 mg/m 2 . Methods This single-arm, open-label, phase II study evaluated patients with cervical cancer receiving NEPA and DEX before weekly cisplatin and concomitant radiotherapy for up to 5 weeks. Safety was assessed during weekly adverse event (AE) assessments. Efficacy was evaluated using Patient Diaries reporting daily nausea, vomiting, and use of rescue medication during the study period. Results Between October 8, 2018, and January 2, 2024, 73 patients were recruited from two Danish departments of oncology; 37 completed all five weekly cycles. The majority of AEs were of mild or moderate intensity, with fatigue being the most frequently observed (95% of patients). Seven (10%) patients encountered ≥ 1 grade 3 treatment-related AEs (TRAEs). No grade 4 TRAEs or deaths were observed. In terms of efficacy, no vomiting and no nausea days 1–35 were 86% and 18%, respectively. Mean time to first emetic episode was 9 days. Conclusion Weekly NEPA administration was safe, well-tolerated, and highly effective during concomitant radiotherapy and weekly cisplatin. Trial registration This trial is registered at ClinicalTrials.gov (NCT03668639-2018–09-10).

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