HPV Vaccine Safe for Young Survivors of Cancer
Only 55% of U.S. adolescents are up-to-date on the recommended immunization schedule against human papillomavirus (HPV), well below the Healthy People 2030 goal of 80%. This low uptake is particularly of concern in young cancer survivors, whose risk of new cancers, including the cancers related to HPV, is higher than that of the general population.
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A study conducted by researchers from Emory University and the University of Alabama at Birmingham assessed the effectiveness, immunogenicity, and safety of the HPV vaccine in adolescent and young adult cancer survivors. The phase 2, single-arm, open-label, noninferiority trial enrolled 453 cancer survivors between ages 9 and 26, who had completed cancer treatment from 1 to 5 years previously and were considered in remission, who hadn’t received the HPV vaccine. The participants received three IM doses of either the quadrivalent vaccine (HPV4) or the nonavalent vaccine (HPV9), with mean age at first dose of 15.6 years. Data from published trials of the HPV vaccine in similar-age subjects (n = 26,486) were used as comparison. The study examined antibody response to the oncogenic HPV types 16 and 18 at month 7. Responses in the tested participants were considered noninferior if the lower bound of the adjusted 95% confidence interval was greater than 0.5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titers (GMT) in cancer survivors when compared to the general population.
Responses were determined for male and female participants, and by age group (ages 9 to 15 and 16 to 26). The ratio of mean GMT for anti-HPV-16 and anti-HPV-18 in survivors versus the general population was greater than 1 for all subgroups in both vaccine cohorts, ranging from 1.64 for anti-HPV-16 in females ages 9 to 15 who received HPV9 to 4.77 for anti-HPV-18 in males ages 16 to 26 who received HPV4. Noninferiority criteria were met for each age and sex subgroup, except for anti-HPV-18 in females ages 16 to 26 who received HPV9. The safety profile among cancer survivors is also similar to that of the general population, with one or more adverse effects reported by 55% of participants: 51% who received HPV4 and 59% who received HPV9.
These results provide evidence for use in this clinically vulnerable population and can encourage clinicians to discuss the HPV vaccine with cancer survivors. (Landier, W., et al. (2021). Immunogenicity and safety of the human papillomavirus vaccine in young survivors of cancer in the USA: A single-arm, open-label, phase 2, non-inferiority trial. Lancet Child Adolesc Health. Advance online publication. Retrieved December 2021 from https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00278-9/fulltext; Brewer, N. T., et al. (2021). Human papillomavirus vaccination for young survivors of cancer. Lancet Child Adolesc Health. Advance online publication. Retrieved December 2021 from https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00312-6/fulltext)
Released: December 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Nivolumab Improves Survival in Relapsed Malignant Mesothelioma
The CONFIRM trial is the first phase 3 trial to examine survival in patients with pleural or peritoneal mesothelioma whose disease had progressed after platinum-based chemotherapy. It demonstrated longer progression-free survival and overall survival with the anti-PD-L1 antibody nivolumab compared with placebo. Malignant mesothelioma is a universally lethal cancer that is usually caused by exposure to asbestos fibers. Since 2004, when pemetrexed and cisplatin were approved for treatment of pleural mesothelioma, no other agent has shown improved survival after disease progression in patients with the cancer.
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The study enrolled 333 patients with mesothelioma and ECOG performance status of 0-1, who had previously received first-line platinum chemotherapy and had radiologic evidence of disease progression. Mean age of patients was 70 years, with 76% male and 80% with ECOG status of 1; 316 patients (95%) had pleural mesothelioma, 293 (88%) had epithelioid histology, and 230 (69%) had been exposed to asbestos. All patients had received platinum-based chemotherapy; 97% had received pemetrexed. They were assigned to 240-mg nivolumab over 30 minutes IV every 2 weeks until disease progression or 12 months (n = 221) or to placebo (n = 111). Participants were assessed with computed tomography scans on day 1 of each 2-week cycle and 4 weeks after treatment discontinuation.
Median follow-up was 11.6 months. By the date of preliminary analysis, 210 (63%) of the patients had experienced disease progression. Median progression-free survival in the nivolumab group was 3.0 months, compared to 1.8 months in the placebo group (hazard ratio [HR], 0.67). Progression-free survival at 1 year was 14.2% in the nivolumab group vs. 7.2% in the placebo group. Median overall survival in the nivolumab group was 10.2 months, compared to 6.9 months in the placebo group (HR, 0.69). Overall survival at 1 year was 43.4% in the nivolumab group vs. 30.1% in the placebo group. The overall response rate was significantly higher in the nivolumab group: 25 patients (11%) had a partial response compared to 1 (1%) in the placebo group. The most frequently reported grade 3 or worse treatment-related adverse events were diarrhea (6 patients [3%] with nivolumab and 2 patients [2%] with placebo) and infusion-related reactions (6 patients [3%] with nivolumab). (Fennell, D. A., et al. (2021). Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): A multicenter, double-blind, randomized, phase 3 trial. Lancet Oncol, 22(11), 1530–1540. Retrieved December 2021 from https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00471-X/fulltext#seccestitle10)
Released: December 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Anticoagulant and Antiplatelet Treatments Associated with Lower Mortality Among Critically Ill COVID-19 Patients
Early in the pandemic, the mortality rate among critically ill patients was about 50%, but over time, there has been a downward trend in mortality, to between 19% and 40%. Effective treatments for the complications of the viral disease are among the factors responsible for that decline, so quantifying the effectiveness of various treatments used in critically ill patients is essential. A 1-year retrospective cohort study that examined all patients (n = 2,070) admitted to ICUs during the study period in six hospitals affiliated with the Yale-New Haven Health System aimed to identify treatments associated with lower COVID-19 mortality based on multivariable analysis and then to evaluate that finding by propensity score-matching analysis.
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Treatments studied included any COVID-related pharmacologic or organ support interventions initiated during hospitalization, including antivirals, anticoagulants, antiplatelets, steroids, immunomodulators, immunosuppressants, vasopressors, oxygen therapy delivered through nasal cannula or face mask, bilevel positive airway pressure, continuous positive airway pressure, mechanical ventilation, venovenous hemofiltration, and extracorporeal membrane oxygenation. Potential confounders included in the analysis were known risk factors for COVID, the severity of the acute illness during the first 24 hours after ICU admission, and the various phases of the pandemic. The final analysis included 856 patients (41%) admitted to the ICU during phase 1; 138 (6.7%) during phase 2; 400 (19.3%) during phase 3; and 676 (32.7%) during phase 4. Of the 2,070 patients, 593 died during hospitalization, and 1,477 were discharged alive.
The treatments identified as being associated with lower mortality on multivariable analysis included the antiviral atazanavir; the anticoagulants enoxaparin, heparin, and apixaban; the antiplatelet aspirin; famotidine; and oxygen therapy. But after multiple testing corrections, only apixaban and aspirin remained significantly associated with lower mortality.
Apixaban treatment was associated with a 52% lower mortality risk. Propensity-score matching analysis with apixaban examined 360 pairs of patients; mortality risk in those treated with apixaban was 27% vs. 37% in the matched cohort not treated with apixaban (hazard ratio [HR], 0.48). Enoxaparin was the anticoagulant of choice for hospitalized COVID patients; in total, 72.7% of patients received enoxaparin, whereas only 19.7% received apixaban. Although multivariable analysis suggested an association between enoxaparin treatment and lower mortality, this result was no longer significant after multiple testing correction. Antiplatelet treatment with aspirin was associated with a 43% lower mortality risk. On propensity-score matching analysis, which examined 473 pairs, mortality risk in those treated with aspirin was 26% vs. 30% in the matched cohort not treated with aspirin (HR, 0.57).
Patients admitted to the ICU experienced a much higher risk (30%) of venous thromboembolism than other hospitalized COVID patients (13%). These results suggest taking a more proactive approach toward use of these drugs and in increasing the use of apixaban, to ease the burden of severe COVID disease. (Zhao, X., et al. (2021). Treatments associated with lower mortality among critically ill covid-19 patients: A retrospective cohort study. Anesthesiology, 135, 1076–1090. Retrieved December 2022 from https://pubs.asahq.org/anesthesiology/article/135/6/1076/117698/Treatments-Associated-with-Lower-Mortality-among)
Released: December 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer