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Background The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. Clinical Trials Registration EudraCT, 2020-004123-16.

Thailand and China’s internet penetration rates have rocketed over the past 15 years. Such increased access has led to increased scholarly interest in students’ online gaming habits in both countries. However, there is little research availablea bout how undergraduate students in both countries consider their own and their peers’ gaming attitudes and habits, especially when these are sensitively aligned with “addiction.” Lacking too is research about how they think gaming impacts learning and academic performance between students from different university disciplines. This research examines undergraduate students in Thailand and China from the humanities compared with those from other disciplines in respect to their attitudes to and awareness of gaming addiction. A sample of 181 students from international and private universities were surveyed. Their interactions with leading games were analysed. A Likert scale was used alongside open-response questions and qualitative discourse analysis forming a mixed method to interpret these results. It is shown in this descriptive-inferential study that that students’ field of study, whether they actively played games and how often they played games all impacted how they valued their own gaming and defined the concept of “addiction.” Humanities and science students showed the same gaming habits as per daily hours spent gaming; business/economics students gamed less overall.Those who considered themselves addicted to gaming, perceived gaming addiction to account for 15-21hours spent gaming per week. Threshold gaming hours, positive and negative aspects of over gaming and a variance between moral and aesthetic appreciation of gaming as it impacts gamers’' lives were noted. Tanto Tailandia como China han experimentado un aumento significativo en las tasas de penetración de internet en los últimos 15 años. Este mayor acceso ha llevado a un aumento del interés académico en los hábitos de juego en línea de los estudiantes en ambos países. Sin embargo, hay poca investigación disponible sobre cómo los estudiantes universitarios en ambos países consideran sus propias actitudes y hábitos de juego, así como los de sus compañeros, especialmente cuando estos están sensiblemente relacionados con la "adicción". También falta investigación sobre cómo creen que los videojuegos afectan el aprendizaje y el rendimiento académico entre estudiantes de diferentes disciplinas universitarias. Este estudio examina a estudiantes universitarios de Tailandia y China en el área de humanidades en comparación con aquellos de otras disciplinas en relación con sus actitudes y conciencia sobre la adicción a los videojuegos. Se encuestó a una muestra de 181 estudiantes de universidades internacionales y privadas. Se analizaron sus interacciones con los juegos líderes. Se utilizó una escala de Likert junto con preguntas abiertas y análisis cualitativo dediscurso para interpretar estos resultados. Este estudio descriptivo-inferencial muestra que el campo de estudio de los estudiantes, si juegan juegos activamente y con qué frecuencia juegan, impactó en cómo valoran su propio juego y definen el concepto de"adicción". Los estudiantes de humanidades y ciencias mostraron los mismos hábitos de juego en términos de horas diarias dedicadas al juego; los estudiantes de negocios/economía jugaron menos en general. Aquellos que se consideraron adictos al juego, percibieron que la adicción al juego representaba entre 15 y 21 horas de juego por semana. Se observaron umbrales de horas de juego, aspectos positivos y negativos de jugar en exceso, y una variación entre la apreciación moral y estética del juego y cómo afecta la vida de los jugadores.

BackgroundThe recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported.MethodsAdults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.ResultsOf 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.ConclusionsA 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated.

BackgroundOmicron-containing bivalent boosters are available worldwide. Results of a large, randomized, active-controlled study are presented.MethodsThis phase 3, randomized, observer-blind, active-controlled trial in the United Kingdom evaluated the immunogenicity and safety of 50-µg doses of omicron-BA.1-monovalent mRNA-1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50-µg mRNA-1273 administered as boosters in individuals ≥16 years. Participants had previously received 2 doses of any authorized/approved Covid-19 vaccine with or without an mRNA vaccine booster. Safety and immunogenicity were primary objectives; immunogenicity was assessed in all participants, with analysis conducted based on prior infection status. Incidence of Covid-19 post-boost was a secondary (mRNA-1273.214) or exploratory (mRNA-1273.529) objective.ResultsIn part 1 of the study, 719 participants received mRNA-1273.529 (n=362) or mRNA-1273 (n=357); in part 2, 2813 received mRNA-1273.214 (n=1418) or mRNA-1273 (n=1395). Median durations (months [interquartile range]) between the most recent Covid-19 vaccine and study boosters were similar in the mRNA-1273.529 (4.0 [3.6-4.7]) and mRNA-1273 (4.1 [3.5-4.7]) (part 1), and mRNA-1273.214 (5.5 [4.8-6.2] and mRNA-1273 (5.4 [4.8-6.2]) groups (part 2).Both mRNA-1273.529 and mRNA-1273.214 elicited superior neutralizing antibody responses against omicron BA.1 with geometric mean ratios (99% CIs) of 1.68 (1.45-1.95) and 1.53 (1.41-1.67) compared to mRNA-1273 at day 29 post-boost. Although the study was not powered to assess relative vaccine efficacy, the incidence rates/1000 person years (95% CI) of Covid-19 trended lower with mRNA-1273.529 (670.5 [528.3-839.3]) than mRNA-1273 (769.3 [615.4-950.1]) and mRNA-1273.214 (633.0 [538.1-739.7]) than mRNA-1273 (711.6 [607.5-828.5]).Sequence analysis in part 2 showed that this was driven by lower incidence of Covid-19 in the mRNA-1273.214 cohort with BA.2 and BA.4 sublineages but not BA.5 sublineages. All study boosters were well-tolerated.ConclusionThe bivalent omicron BA.1-containing booster elicited superior neutralizing antibody responses against omicron BA.1 with acceptable safety results consistent with the BA.1 monovalent vaccine. Incidence rates for Covid-19 were numerically lower in participants who received mRNA-1273.214 compared to the original booster vaccine mRNA-1273, driven by the BA.2 and BA.4 sublineages.

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

BackgroundThe Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine.MethodsIn this immunobridging phase 3 trial (COV-COMPARE), participants aged 18 years and older who were medically stable (as determined by an investigator) were enrolled at 26 sites in the UK. In the double-blind, randomised, controlled arm of the trial, participants aged 30 years and older were randomly assigned (2:1) to receive two doses of VLA2001 (0·5 mL; with 33 antigen units [AU] per dose) or ChAdOx1-S (0·5 mL; with 2·5 × 108 infectious units per dose) on days 1 and 29. In another arm, participants aged 18–29 years received two doses of VLA2001 (same dose) open label on days 1 and 29. The primary immunogenicity outcome was the immune response of a two-dose schedule of VLA2001 on day 43, in adults aged 30 years and older, versus two doses of ChAdOx1-S via superiority of geometric mean titres (GMTs) of neutralising antibodies (GMT ratio of >1 at a two-sided significance level of 5%) and non-inferiority of the seroconversion rate (non-inferiority margin of –10% for the lower limit of the 95% CI for the difference between groups). The primary safety outcome was the frequency and severity of any adverse events in all participants up to day 43. Safety was assessed in all participants who received at least one dose of vaccine. GMTs were assessed in a subset of participants aged 30 years and older who were seronegative at baseline, had at least one evaluable antibody titre measurement after vaccination, and had no confirmed COVID-19 during the study (immunogenicity population); and seroconversion was assessed in the per-protocol population, which comprised the immunogenicity population but excluding any participants with major protocol violations. For each timepoint, only participants with available data were included in the analysis. This study is registered with ClinicalTrials.gov, NCT04864561, and is ongoing.FindingsBetween April 28 and June 3, 2021, 4181 individuals were screened and 4017 enrolled, of whom 2975 (74%) were aged 30 years or older and randomly assigned to receive VLA2001 (n=1978) or ChAdOx1-S (n=997), and 1042 (26%) were aged 18–29 years (all received open-label VLA2001). 4012 participants received at least one dose of vaccine (1040 in the open-label VLA2001 group, 1977 in the randomised VLA2001 group, and 995 in the ChAdOx1-S group). The immunogenicity population comprised 492 participants in the randomised VLA2001 group and 498 in the ChAdOx1-S group; three participants in the VLA2001 group were excluded from the per-protocol population. VLA2001 induced higher neutralising GMTs than did ChAdOx1-S (803·5 [95% CI 748·5–862·6] vs 576·6 [543·6–611·7]; GMT ratio 1·39 [95% CI 1·25–1·56]; pInterpretationVLA2001 has a favourable tolerability profile and met superiority criteria for neutralising antibodies and non-inferiority criterion for seroconversion rates compared with ChAdOx1-S. The data presented here formed the basis of successful marketing approval for use of VLA2001 in primary vaccination in the EU, the UK, Bahrain, and United Arab Emirates.

Patients with reciprocal balanced translocations (RBT) have a risk for recurrent pregnancy losses (RPL), affected child, and infertility. Currently, genetic counseling is based on karyotypes found among the products of conception (POC), although factors influencing the success of assisted reproductive technologies (ART) in RBT couples are not established. Cytogenetic results from 261 POC and offspring of the parents (113 women and 90 men) with RBT were evaluated. Chromosome segregation modes and number of euploid embryos were assessed in couples undergoing in vitro fertilization. Patients with translocations involving an acrocentric chromosome have a higher risk of unbalanced gametes caused by a 3:1 segregation. Female RBT patients have a statistically higher risk of aneuploidy due to an interchromosomal effect. The rate of euploid embryos is low due to meiosis I malsegregation of RBT, meiosis II nondisjunction, additional whole chromosome or segmental aneusomies. RBT patients with RPL have a higher rate of miscarriage of euploid fetuses with RBT. Chromosome-specific factors, female gender, age, and history of RPL are the risk elements influencing pregnancy and in vitro fertilization success in RBT patients. Chromosomal microarray analysis of POC is necessary to provide an accurate and timely diagnosis for patients with adverse reproductive outcomes.

Aim: In the absence of comparative studies, guidelines consider neurokinin 1 receptor antagonists (RAs) as interchangeable. We evaluated the pooled efficacy from three cisplatin registration trials, each with arms containing netupitant/palonosetron (NEPA), a fixed neurokinin 1 RA (netupitant)/serotonin Type 3 (5-HT3) RA (palonosetron) combination, and an aprepitant (APR) regimen. Materials & methods: Efficacy data were pooled for rates of complete response (CR: no emesis/no rescue medication), complete protection (CR + no significant nausea), total control (CR + no nausea) and no significant nausea during acute (0–24 h), delayed (>24–120 h) and overall (0–120 h) phases post chemotherapy. Results: Among 621 NEPA and 576 APR patients, response rates were similar for the acute phase, and generally favored NEPA during delayed and overall phases. CR rates for NEPA versus APR were 88.4 versus 89.2%, 81.8 versus 76.9% (p

Graduate students from the Culture, Learning, and Technology division recently hosted a webinar on critical theories and how they may be applied in learning design and research. This article presents an introduction to some of the challenges and opportunities in using critical perspectives in our work, and in our field, that emerged from the webinar discussions.

Purpose Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. Materials and Methods We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. Results Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. Conclusions Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. Implications for Practice After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.

PURPOSE To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors (CPIs). METHODS ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy. RESULTS The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non–small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor–containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients. RECOMMENDATIONS Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic. Additional information is available at www.asco.org/supportive-care-guidelines .

Background: Anthracycline and cyclophosphamide (AC) is a highly emetogenic chemotherapy (HEC) regimen. Combination netupitant/palonosetron (NEPA) + dexamethasone (DEX) is guideline-recommended for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in HEC and moderately emetogenic chemotherapy. CMS’ OP-35 measure deems 30-day post-chemotherapy acute care as avoidable if involving nausea and emesis (NV) or any of 8 other toxicities. Results will be publicly reported and impact Medicare reimbursement. CMS (2017) found that 10% of >58,000 patients with avoidable acute care after chemotherapy involved NV. Because NEPA is new, insufficient real world data exist to assess its CINV resource use. CINV-related acute-care after NEPA prophylaxis in AC has been reported in a prospective clinical trial. Our aim was to compare these rates to those seen after prophylaxis with other antiemetics for AC outside of a clinical trial. Methods: Pre-specified endpoints in a prospective trial of oral or IV NEPA + DEX in AC included acute-care use (emergency [ED] visits or inpatient admissions [IP]) involving CINV, defined as emesis or rescue drug use ≤5 days after AC, and concomitant ED/IP in the same period. We also evaluated CINV-related acute care after non-NEPA prophylaxis for AC in breast cancer from 10/2012-8/2018 in IBM Explorys electronic health records. We age-matched patients 3:1 to the NEPA trial. We further adjusted the event rate to address under-reporting of a) CINV rates (vs. 49.2% for aprepitant in AC in a clinical trial [Warr 2005]) and b) acute-care use, projected at 17-50% at sites external to the dataset. To compare the resulting adjusted event rate to the NEPA study, we conducted 10,000 Monte Carlo simulations, using random probabilities from 5.2-8.7% for Explorys patients, and from 0-2% for NEPA patients to address potential reporting variability, despite the trial including daily patient diaries. Analysis of data was limited to the first two cycles, the median duration in the NEPA trial. Results: In the NEPA trial, 402 patients received ≥1 cycle; 391 completed two cycles. Nine patients had IP admissions; none involved CINV. Five patients had 6 total ED visits; one met criteria for involving CINV; the resulting rate of acute care rate involving CINV was 0.25 per 100 patients. For other antiemetics, 2598 patients received AC (excluding NEPA prophylaxis). Among 1206 age-matched to the NEPA trial, 15 patients had acute-care events in the first 2 cycles, (1.24 per 100 patients), an odds ratio of 1:5.1 (CI 0.7-38.5) in favor of NEPA. After adjusting via the simulation, the odds ratio was 1:8.3 (CI: 2.43-24.21) in favor of NEPA. Conclusions: Comparing CINV-related acute care seen in a large prospective trial relative to real-world evidence in patients with breast cancer treated with AC, Citation Format: Lee Schwartzberg, Kathryn J Ruddy, Rudolph M Navari, Thomas W LeBlanc, Rebecca Clark-Snow, Rita Wickham, Gary Binder, William L. Bailey, Ravi Potluri, Luke M Schmerold, Eros Papademetriou, Eric J Roeland. Avoidable acute care involving chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer receiving anthracycline + cyclophosphamide (AC) with NEPA prophylaxis relative to other antiemetics: An external control arm analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-07.

Background NEPA, a combination antiemetic of a neurokinin‐1 (NK1) receptor antagonist (RA) (netupitant [oral]/fosnetupitant [intravenous; IV]) and 5‐HT3RA, palonosetron] offers 5‐day CINV prevention with a single dose. Fosnetupitant solution contains no allergenic excipients, surfactant, emulsifier, or solubility enhancer. A phase III study of patients receiving cisplatin found no infusion‐site or anaphylactic reactions related to IV NEPA. However, hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, particularly fosaprepitant in patients receiving anthracycline‐cyclophosphamide (AC)‐based chemotherapy. This study evaluated the safety and efficacy of IV NEPA in the AC setting. Materials and Methods This phase IIIb, multinational, randomized, double‐blind study enrolled females with breast cancer naive to highly or moderately emetogenic chemotherapy. Patients were randomized to receive a single 30‐minute infusion of IV NEPA or single oral NEPA capsule on day 1 prior to AC, in repeated (up to 4) cycles. Oral dexamethasone was given to all patients on day 1 only. Results A total of 402 patients were included. The adverse event (AE) profiles were similar for IV and oral NEPA and consistent with those expected. Most AEs were mild or moderate with a similarly low incidence of treatment‐related AEs in both groups. There were no treatment‐related injection‐site AEs and no reports of hypersensitivity or anaphylaxis. The efficacy of IV and oral NEPA were similar, with high complete response (no emesis/no rescue) rates observed in cycle 1 (overall [0–120 hours] 73.0% IV NEPA, 77.3% oral NEPA) and maintained over subsequent cycles. Conclusion IV NEPA was highly effective and safe with no associated hypersensitivity and injection‐site reactions in patients receiving AC. Implications for Practice As a combination of a neurokinin‐1 (NK1) receptor antagonist (RA) and 5‐HT3RA, NEPA offers 5‐day chemotherapy‐induced nausea and vomiting prevention with a single dose and an opportunity to improve adherence to antiemetic guidelines. In this randomized multinational phase IIIb study, intravenous (IV) NEPA (fosnetupitant/palonosetron) was safe and highly effective in patients receiving multiple cycles of anthracycline‐cyclophosphamide (AC)‐based chemotherapy. Unlike other IV NK1RAs, the IV NEPA combination solution does not require any surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. Hypersensitivity reactions and anaphylaxis have been reported with other IV NK1RAs, most commonly with fosaprepitant in the AC setting. Importantly, there were no injection‐site or hypersensitivity reactions associated with IV NEPA., Netupitant and palonosetron (NEPA) is a combination antiemetic that offers five‐day prevention of chemotherapy‐induced nausea and vomiting with a single dose. This article evaluates the safety and efficacy of intravenous NEPA in the setting of anthracycline/cyclophosphamide chemotherapy.

BackgroundCovid-19 vaccines are urgently needed, especially against emerging variants. NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 rS) nanoparticle vaccine containing trimeric full-length SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant.MethodsA phase 3, randomized, observer-blinded, placebo-controlled trial was conducted in adults 18-84 years old who received two intramuscular 5-µg doses, 21 days apart, of NVX-CoV2373 or placebo (1:1) across 33 sites in the United Kingdom. The primary efficacy endpoint was virologically confirmed symptomatic Covid-19 with onset 7 days after second vaccination in serologically negative participants.ResultsA total of 15,187 participants were randomized, of whom 7569 received NVX-CoV2373 and 7570 received placebo; 27.2% were 65 years or older, 44.7% had comorbidities and 4.2% had baseline serological evidence of SARS-CoV-2. There were 10 cases of Covid-19 among NVX-CoV2373 recipients and 96 cases among placebo recipients, with symptom onset at least 7 days after second vaccination; NVX-CoV2373 was 89.7% (95% confidence interval, 80.2 to 94.6) effective in preventing Covid-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8 to 99.5) and 86.3% (71.3 to 93.5) against the prototype strain and B.1.1.7 variant, respectively. Vaccine efficacy was similar across subgroups, including participants with comorbidities and those ≥65 years old. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups.ConclusionA two-dose regimen of NVX-CoV2373 conferred 89.7% protection against a blend of prototype and variant Covid-19, demonstrated high efficacy against the B.1.1.7 variant, and had a reassuring safety profile.(Funded by Novavax, Inc. EudraCT number, 2020-004123-16).