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In this trial involving more than 24,000 participants, the efficacy of two doses of a viruslike-particle, plant-based vaccine with adjuvant was 69.5% against symptomatic Covid-19 and 78.8% against moderate-to-severe disease. More than 80% of vaccine recipients had local or systemic adverse effects, which were generally mild and short-lived.

When the adjuvanted HZ subunit vaccine candidate was coadministered with a quadrivalent seasonal influenza vaccine, no interference in the immune responses were observed, and no safety concerns were identified. Abstract Background The immunogenicity and safety of an adjuvanted herpes zoster subunit (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years. Methods Subjects were randomized 1:1 to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control group). The primary objectives were the HZ/su vaccine response rate in the coadministration group and the noninferiority of the antibody responses to HZ/su and IIV4 in the coadministration compared with the control group. Safety information was collected throughout the duration of the study. Results A total of 413 subjects were vaccinated in the coadministration group and 415 in the control group. The HZ/su vaccine response rate in the coadministration group was 95.8% (95% confidence interval, 93.3%–97.6%) and the anti–glycoprotein E GMCControl/Coadmin ratio was 1.08 (.97–1.20). The primary noninferiority objectives were met. No safety concerns were observed. Conclusions No interference in the immune responses to either vaccine was observed when the vaccines were coadministered, and no safety concerns were identified. Clinical Trials Registration NCT01954251.

Improved survival in renal-cell cancer after 1 year of adjuvant therapy was seen with pembrolizumab. At 4 years, 91% of pembrolizumab-treated patients were alive, as compared with 86% of those who received placebo after surgery.

Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines. This phase I, randomized, double-blind trial evaluated the safety and immunogenicity of one dose of 2018/2019 quadrivalent influenza vaccine (either Fluzone® or Flublok®) administered intramuscularly with or without one of two adjuvants (AF03 or Advax-CpG55.2). A total of 241 healthy adults aged 18–45 years were enrolled and randomized to 1 of 6 groups. Groups 1–3 received one dose of Fluzone® QIV 2018/2019 administered alone or with AF03 or Advax-CpG55.2 and Groups 4–6 received one dose of Flublok® QIV 2018/2019 alone or with one of these two adjuvants. All participants received Fluzone® or Flublok® QIV 2019/2020 ninety days later. Primary objectives were to evaluate safety and reactogenicity along with changes in hemagglutinin inhibition (HAI), neuraminidase inhibition (NAI) and neutralizing antibodies to 2018/2019 seasonal influenza antigens, comparing Day 1 and Day 29 titers. Secondary objectives evaluated the impact of adjuvants on immune responses after subsequent doses of unadjuvanted seasonal influenza vaccine and immunologic responses to heterologous influenza H1 and H3 antigens. Overall, the adjuvanted vaccines were safe and generated robust immune responses against both homologous and heterologous strains. Similar responses were seen across all six study arms. Both adjuvants were associated with qualitatively improved immune responses against some strains at varying timepoints, but results were inconsistent. There were no substantial differences in safety or reactogenicity identified between the study groups and all vaccine formulations were well tolerated. In this highly immunologically-experienced cohort, neither AF03 nor Advax-CpG55.2 demonstrated notable benefit when added to the seasonal influenza vaccine. (ClinicalTrials.gov ID# NCT03945825). •First human study to use the combination of Advax and CpG55.2 as an adjuvant.•Vaccine candidates induced robust antibody responses to multiple influenza strains.•Each of the vaccine candidates were safe and well-tolerated.•High baseline immunity may have overshadowed potential adjuvant effects.•Not adequately powered to identify significant differences between adjuvants.

In a randomized trial involving more than 900 patients undergoing resection of advanced melanoma, adjuvant nivolumab was associated with a higher rate of 12-month recurrence-free survival than ipilimumab (70.5% vs. 60.8%) and with fewer adverse events.

Respiratory syncytial virus causes clinically significant illness in children and adults. In a placebo-controlled trial, a prefusion stabilized F protein vaccine led to an 83% lower risk of RSV infection.

Patients with resectable lung cancer were assigned to neoadjuvant pembrolizumab or placebo plus chemotherapy and adjuvant pembrolizumab or placebo. Two-year event-free survival was 62.4% with pembrolizumab and 40.6% with placebo.

Cardiorespiratory fitness is an independent risk factor for cardiovascular disease and shortened life expectancy in breast cancer survivors. This randomised controlled trial (n = 153) was designed for patients with a physically inactive lifestyle prediagnosis and concurrently referred to adjuvant chemotherapy. We compared two 12-week exercise interventions aimed at physiological and patient-reported outcomes (cardiorespiratory fitness, muscle strength, metabolic markers, physical activity, pain, fatigue), including a 39-week follow-up. A supervised hospital-based moderate to high intensity group exercise intervention was compared to an instructed home-based individual pedometer intervention. The two 12-week interventions included oncologists’ recommendations and systematic health counselling. Outcomes were measured at baseline and week 6, 12 and 39. Primary outcome cardiorespiratory fitness declined significantly during chemotherapy and was restored in both interventions at follow-up. The interventions effectively engaged breast cancer patients in sustaining physical activities during and following adjuvant treatment. A composite metabolic score improved significantly. Positive cardiorespiratory fitness responders had improved clinical effects on fatigue, pain and dyspnoea versus negative responders. We conclude that a loss of cardiorespiratory fitness among physically inactive breast cancer patients may be restored by early initiated interventions and by adapting to physical activity recommendations, leading to a decreased cardiovascular risk profile in breast cancer survivors.

Patients with surgically resected stage III melanoma are at high risk for recurrence. The 5-year survival rate with ipulimumab was 11 percentage points higher than that with placebo (65% vs. 54%), but there were substantial immune-related toxic effects. Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4) to augment antitumor immune responses, was approved by the Food and Drug Administration (FDA) and the European Medicines Agency in 2011 at a dose of 3 mg per kilogram of body weight for the treatment of advanced melanoma. 1 , 2 On the basis of data from a phase 2 trial that indicated the potential for a dose of 10 mg per kilogram to have higher efficacy than the dose of 0.3 mg or 3 mg per kilogram in patients with advanced melanoma, although at a cost of more . . .

S-1 has shown promising efficacy with a mild toxicity profile in patients with advanced biliary tract cancer. The aim of this study was to evaluate whether adjuvant S-1 improved overall survival compared with observation for resected biliary tract cancer. This open-label, multicentre, randomised phase 3 trial was conducted in 38 Japanese hospitals. Patients aged 20–80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone no local residual tumour resection or microscopic residual tumour resection were randomly assigned (1:1) to undergo observation or to receive S-1 (ie, 40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice daily for 4 weeks, followed by 2 weeks of rest for four cycles). Randomisation was performed by the minimisation method, using institution, primary tumour site, and lymph node metastasis as adjustment factors. The primary endpoint was overall survival and was assessed for all randomly assigned patients on an intention-to-treat basis. Safety was assessed in all eligible patients. For the S-1 group, all patients who began the protocol treatment were eligible for a safety assessment. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry (UMIN000011688). Between Sept 9, 2013, and June 22, 2018, 440 patients were enrolled (observation group n=222 and S-1 group n=218). The data cutoff date was June 23, 2021. Median duration of follow-up was 45·4 months. In the primary analysis, the 3-year overall survival was 67·6% (95% CI 61·0–73·3%) in the observation group compared with 77·1% (70·9–82·1%) in the S-1 group (adjusted hazard ratio [HR] 0·69, 95% CI 0·51–0·94; one-sided p=0·0080). The 3-year relapse-free survival was 50·9% (95% CI 44·1–57·2%) in the observation group compared with 62·4% (55·6–68·4%) in the S-1 group (HR 0·80, 95% CI 0·61–1·04; two-sided p=0·088). The main grade 3–4 adverse events in the S-1 group were decreased neutrophil count (29 [14%]) and biliary tract infection (15 [7%]). Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients. The National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.